{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:30:37Z","timestamp":1789774237469,"version":"4.0.1"},"reference-count":192,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Houston","award":["R01EY029289"],"award-info":[{"award-number":["R01EY029289"]}]},{"name":"National Institute of Health\/National Eye Institute","award":["R01EY029289"],"award-info":[{"award-number":["R01EY029289"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The cornea is continuously exposed to injuries, ranging from minor scratches to deep traumas. An effective healing mechanism is crucial for the cornea to restore its structure and function following major and minor insults. Transforming Growth Factor-Beta (TGF-\u03b2), a versatile signaling molecule that coordinates various cell responses, has a central role in corneal wound healing. Upon corneal injury, TGF-\u03b2 is rapidly released into the extracellular environment, triggering cell migration and proliferation, the differentiation of keratocytes into myofibroblasts, and the initiation of the repair process. TGF-\u03b2-mediated processes are essential for wound closure; however, excessive levels of TGF-\u03b2 can lead to fibrosis and scarring, causing impaired vision. Three primary isoforms of TGF-\u03b2 exist\u2014TGF-\u03b21, TGF-\u03b22, and TGF-\u03b23. Although TGF-\u03b2 isoforms share many structural and functional similarities, they present distinct roles in corneal regeneration, which adds an additional layer of complexity to understand the role of TGF-\u03b2 in corneal wound healing. Further, aberrant TGF-\u03b2 activity has been linked to various corneal pathologies, such as scarring and Peter\u2019s Anomaly. Thus, understanding the molecular and cellular mechanisms by which TGF-\u03b21-3 regulate corneal wound healing will enable the development of potential therapeutic interventions targeting the key molecule in this process. Herein, we summarize the multifaceted roles of TGF-\u03b2 in corneal wound healing, dissecting its mechanisms of action and interactions with other molecules, and outline its role in corneal pathogenesis.<\/jats:p>","DOI":"10.3390\/cells13131105","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T05:03:07Z","timestamp":1719378187000},"page":"1105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["TGF-\u03b2-Based Therapies for Treating Ocular Surface Disorders"],"prefix":"10.3390","volume":"13","author":[{"given":"Fernando T.","family":"Ogata","sequence":"first","affiliation":[{"name":"College of Optometry, University of Houston, 4901 Calhoun Road, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-1987","authenticated-orcid":false,"given":"Sudhir","family":"Verma","sequence":"additional","affiliation":[{"name":"College of Optometry, University of Houston, 4901 Calhoun Road, Houston, TX 77204, USA"},{"name":"Deen Dayal Upadhyaya College, University of Delhi, Delhi 110078, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5848-0225","authenticated-orcid":false,"given":"Vivien J.","family":"Coulson-Thomas","sequence":"additional","affiliation":[{"name":"College of Optometry, University of Houston, 4901 Calhoun Road, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0136-0986","authenticated-orcid":false,"given":"Tarsis F.","family":"Gesteira","sequence":"additional","affiliation":[{"name":"College of Optometry, University of Houston, 4901 Calhoun Road, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1097\/01.opx.0000192350.01045.6f","article-title":"Automated decision tree classification of corneal shape","volume":"82","author":"Twa","year":"2005","journal-title":"Optom. Vis. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.preteyeres.2015.07.002","article-title":"Progress in corneal wound healing","volume":"49","author":"Ljubimov","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","first-page":"e737","article-title":"Human corneal fibroblast migration and extracellular matrix synthesis during stromal repair: Role played by platelet-derived growth factor-BB, basic fibroblast growth factor, and transforming growth factor-beta1","volume":"12","author":"Garrote","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1167\/iovs.63.13.6","article-title":"Hyaluronan Modulates the Biomechanical Properties of the Cornea","volume":"63","author":"Lin","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mutoji, K.N., Sun, M., Elliott, G., Moreno, I.Y., Hughes, C., Gesteira, T.F., and Coulson-Thomas, V.J. (2021). Extracellular Matrix Deposition and Remodeling after Corneal Alkali Burn in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115708"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4161\/cam.2.4.6772","article-title":"Matrix metalloproteinase (MMP) and TGF beta 1-stimulated cell migration in skin and cornea wound healing","volume":"2","author":"Joo","year":"2008","journal-title":"Cell Adhes. Migr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"800","DOI":"10.5483\/BMBRep.2009.42.12.800","article-title":"Bevacizumab accelerates corneal wound healing by inhibiting TGF-beta2 expression in alkali-burned mouse cornea","volume":"42","author":"Lee","year":"2009","journal-title":"BMB Rep."},{"key":"ref_8","first-page":"899","article-title":"Transforming growth factor-beta (TGF-beta) inhibits epithelial wound healing of organ-cultured rabbit cornea","volume":"97","author":"Nishida","year":"1993","journal-title":"Nippon Ganka Gakkai Zasshi"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108594","DOI":"10.1016\/j.exer.2021.108594","article-title":"TGF beta -1, -2 and -3 in the modulation of fibrosis in the cornea and other organs","volume":"207","author":"Wilson","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_10","first-page":"176","article-title":"The changes of TGF-alpha, TGF-beta 1 and basic FGF messenger RNA expression in rabbit cornea after photorefractive keratectomy","volume":"16","author":"Zhong","year":"2000","journal-title":"Yan Ke Xue Bao"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.exer.2014.09.012","article-title":"The corneal fibrosis response to epithelial-stromal injury","volume":"142","author":"Torricelli","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"174510","DOI":"10.1016\/j.ejphar.2021.174510","article-title":"TGF-beta-induced fibrosis: A review on the underlying mechanism and potential therapeutic strategies","volume":"911","author":"Ong","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1097\/01.ico.0000136668.41000.73","article-title":"TGF-beta signal transduction in corneal wound healing as a therapeutic target","volume":"23","author":"Saika","year":"2004","journal-title":"Cornea"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41433-019-0736-0","article-title":"Biology of corneal fibrosis: Soluble mediators, integrins, and extracellular vesicles","volume":"34","author":"McKay","year":"2020","journal-title":"Eye"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/j.ajpath.2014.03.013","article-title":"Matrix metalloproteinase-9-null mice are resistant to TGF-beta-induced anterior subcapsular cataract formation","volume":"184","author":"Korol","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108610","DOI":"10.1016\/j.exer.2021.108610","article-title":"The functional role of decorin in corneal neovascularization in vivo","volume":"207","author":"Balne","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"L1006","DOI":"10.1152\/ajplung.00015.2014","article-title":"Matrix metalloproteinase-9 activates TGF-beta and stimulates fibroblast contraction of collagen gels","volume":"306","author":"Kobayashi","year":"2014","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12931-022-02105-7","article-title":"Role of matrix metalloprotease-2 and MMP-9 in experimental lung fibrosis in mice","volume":"23","author":"Bormann","year":"2022","journal-title":"Respir. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.exer.2004.05.003","article-title":"TGF-beta1 stimulates production of gelatinase (MMP-9), collagenases (MMP-1, -13) and stromelysins (MMP-3, -10, -11) by human corneal epithelial cells","volume":"79","author":"Kim","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/jcp.21869","article-title":"Cytokines and signaling pathways regulating matrix metalloproteinase-9 (MMP-9) expression in corneal epithelial cells","volume":"221","author":"Gordon","year":"2009","journal-title":"J. Cell Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"110963","DOI":"10.1016\/j.cellsig.2023.110963","article-title":"TGFbeta1-driven SMAD2\/3 phosphorylation and myofibroblast emergence are fully dependent on the TGFbeta1 pre-activation of MAPKs and controlled by maternal leucine zipper kinase","volume":"113","author":"Wang","year":"2024","journal-title":"Cell Signal"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"C1482","DOI":"10.1152\/ajpcell.00084.2024","article-title":"Substance P promotes transforming growth factor-beta-induced collagen synthesis in human corneal fibroblasts","volume":"326","author":"Sugioka","year":"2024","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0092-8674(76)90148-3","article-title":"Membrane receptors for murine leukemia viruses: Characterization using the purified viral envelope glycoprotein, gp71","volume":"8","author":"DeLarco","year":"1976","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1126\/science.150.3698.893","article-title":"Bone: Formation by autoinduction","volume":"150","author":"Urist","year":"1965","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1177\/00220345710500060601","article-title":"Bone morphogenetic protein","volume":"50","author":"Urist","year":"1971","journal-title":"J. Dent. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molcel.2013.06.016","article-title":"A P(E)RM(I)T for BMP signaling","volume":"51","author":"Guo","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cbi.2018.07.008","article-title":"New insights into TGF-beta\/Smad signaling in tissue fibrosis","volume":"292","author":"Hu","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nickel, J., and Mueller, T.D. (2019). Specification of BMP Signaling. Cells, 8.","DOI":"10.3390\/cells8121579"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/cr.2008.302","article-title":"Signaling cross-talk between TGF-beta\/BMP and other pathways","volume":"19","author":"Guo","year":"2009","journal-title":"Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Dituri, F., Cossu, C., Mancarella, S., and Giannelli, G. (2019). The Interactivity between TGFbeta and BMP Signaling in Organogenesis, Fibrosis, and Cancer. Cells, 8.","DOI":"10.3390\/cells8101130"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/jcp.20917","article-title":"Connective tissue growth factor (CTGF\/CCN2) is a downstream mediator for TGF-beta1-induced extracellular matrix production in osteoblasts","volume":"210","author":"Arnott","year":"2007","journal-title":"J. Cell Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ceb.2007.02.015","article-title":"Negative regulation of TGF-beta receptor\/Smad signal transduction","volume":"19","author":"Itoh","year":"2007","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/cr.2008.327","article-title":"Phospho-control of TGF-beta superfamily signaling","volume":"19","author":"Wrighton","year":"2009","journal-title":"Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1242\/jcs.114.24.4359","article-title":"Smad regulation in TGF-beta signal transduction","volume":"114","author":"Moustakas","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1369\/0022155415627681","article-title":"TGF-beta\/SMAD Pathway and Its Regulation in Hepatic Fibrosis","volume":"64","author":"Xu","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/35043051","article-title":"How cells read TGF-beta signals","volume":"1","author":"Massague","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrm3434","article-title":"TGFbeta signalling in context","volume":"13","author":"Massague","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0002-9440(10)62358-9","article-title":"Expression of Smad7 in mouse eyes accelerates healing of corneal tissue after exposure to alkali","volume":"166","author":"Saika","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1167\/iovs.11-7982","article-title":"Substratum topography modulates corneal fibroblast to myofibroblast transformation","volume":"53","author":"Myrna","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"115317","DOI":"10.1016\/j.addr.2024.115317","article-title":"Corneal fibrosis: From in vitro models to current and upcoming drug and gene medicines","volume":"209","author":"Gurdal","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhang, T., Wang, X.F., Wang, Z.C., Lou, D., Fang, Q.Q., Hu, Y.Y., Zhao, W.Y., Zhang, L.Y., Wu, L.H., and Tan, W.Q. (2020). Current potential therapeutic strategies targeting the TGF-beta\/Smad signaling pathway to attenuate keloid and hypertrophic scar formation. Biomed. Pharmacother., 129.","DOI":"10.1016\/j.biopha.2020.110287"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/S0898-6568(02)00058-X","article-title":"Integration of the TGF-beta pathway into the cellular signalling network","volume":"14","author":"Lutz","year":"2002","journal-title":"Cell Signal"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Luo, K. (2017). Signaling Cross Talk between TGF-beta\/Smad and Other Signaling Pathways. Cold Spring Harb. Perspect. Biol., 9.","DOI":"10.1101\/cshperspect.a022137"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Okumura, N., Kay, E.P., Nakahara, M., Hamuro, J., Kinoshita, S., and Koizumi, N. (2013). Inhibition of TGF-beta signaling enables human corneal endothelial cell expansion in vitro for use in regenerative medicine. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058000"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1126\/science.8140412","article-title":"Characterization of type I receptors for transforming growth factor-beta and activin","volume":"264","author":"Yamashita","year":"1994","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"22765","DOI":"10.1074\/jbc.M401350200","article-title":"In the absence of type III receptor, the transforming growth factor (TGF)-beta type II-B receptor requires the type I receptor to bind TGF-beta2","volume":"279","author":"Babitt","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/mrd.1080320204","article-title":"TGF-beta receptors","volume":"32","author":"Massague","year":"1992","journal-title":"Mol. Reprod. Dev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2966-5_1","article-title":"Regulation of TGF-beta Receptors","volume":"1344","author":"Budi","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15919","DOI":"10.1074\/jbc.270.27.15919","article-title":"Cooperative binding of transforming growth factor (TGF)-beta 2 to the types I and II TGF-beta receptors","volume":"270","author":"Rodriguez","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/emboj.2011.54","article-title":"TGF-beta signalling is mediated by two autonomously functioning TbetaRI:TbetaRII pairs","volume":"30","author":"Huang","year":"2011","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0925-5710(96)00542-7","article-title":"TGF-beta receptors and signal transduction","volume":"65","author":"Miyazono","year":"1997","journal-title":"Int. J. Hematol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3143\/geriatrics.36.162","article-title":"Receptors and signal transduction for the TGF-beta related factors","volume":"36","author":"Miyazono","year":"1999","journal-title":"Nihon Ronen Igakkai Zasshi"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1006\/mcbr.2001.0301","article-title":"Regulation of transforming growth factor-beta signaling","volume":"4","author":"Zhu","year":"2001","journal-title":"Mol. Cell Biol. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1146\/annurev.biochem.67.1.753","article-title":"TGF-beta signal transduction","volume":"67","author":"Massague","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14806","DOI":"10.1074\/jbc.M109.079921","article-title":"Ternary complex of transforming growth factor-beta1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily","volume":"285","author":"Radaev","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"30656","DOI":"10.1074\/jbc.271.48.30656","article-title":"Binding affinity of transforming growth factor-beta for its type II receptor is determined by the C-terminal region of the molecule","volume":"271","author":"Qian","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000057358","article-title":"Molecular and cell biology of TGF-beta","volume":"24","author":"Roberts","year":"1998","journal-title":"Miner. Electrolyte Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.trecan.2016.11.008","article-title":"Targeting TGF-beta Signaling in Cancer","volume":"3","author":"Colak","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1093\/abbs\/gmy092","article-title":"TGF-beta signaling in cancer","volume":"50","author":"Gu","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kardalas, E., Maraka, S., Papagianni, M., Paltoglou, G., Siristatidis, C., and Mastorakos, G. (2021). TGF-beta Physiology as a Novel Therapeutic Target Regarding Autoimmune Thyroid Diseases: Where Do We Stand and What to Expect. Medicina, 57.","DOI":"10.3390\/medicina57060621"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1016\/j.cell.2023.07.036","article-title":"TGF-beta signaling in health and disease","volume":"186","author":"Massague","year":"2023","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3109\/08977194.2011.595714","article-title":"TGF-beta signaling in fibrosis","volume":"29","author":"Biernacka","year":"2011","journal-title":"Growth Factors"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/path.5680","article-title":"TGF-beta as a driver of fibrosis: Physiological roles and therapeutic opportunities","volume":"254","author":"Budi","year":"2021","journal-title":"J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1074\/jbc.M208520200","article-title":"Betaglycan expression is transcriptionally up-regulated during skeletal muscle differentiation. Cloning of murine betaglycan gene promoter and its modulation by MyoD, retinoic acid, and transforming growth factor-beta","volume":"278","author":"Riquelme","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1093\/humupd\/dmx016","article-title":"The role of TGF-beta in the pathophysiology of peritoneal endometriosis","volume":"23","author":"Young","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Stuelten, C.H., and Zhang, Y.E. (2021). Transforming Growth Factor-beta: An Agent of Change in the Tumor Microenvironment. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.764727"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Valluru, M., Staton, C.A., Reed, M.W., and Brown, N.J. (2011). Transforming Growth Factor-beta and Endoglin Signaling Orchestrate Wound Healing. Front. Physiol., 2.","DOI":"10.3389\/fphys.2011.00089"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4426","DOI":"10.1158\/0008-5472.CAN-19-3228","article-title":"Cross-talk between SOX2 and TGFbeta Signaling Regulates EGFR-TKI Tolerance and Lung Cancer Dissemination","volume":"80","author":"Kuo","year":"2020","journal-title":"Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1080\/19420862.2015.1115166","article-title":"Development and characterization of human monoclonal antibodies that neutralize multiple TGFbeta isoforms","volume":"8","author":"Bedinger","year":"2016","journal-title":"mAbs"},{"key":"ref_70","first-page":"1405","article-title":"Temporal and spatial distribution of TGF-beta isoforms and signaling intermediates in corneal regenerative wound repair","volume":"24","author":"Huh","year":"2009","journal-title":"Histol. Histopathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"108325","DOI":"10.1016\/j.exer.2020.108325","article-title":"TGFbeta1 and TGFbeta2 proteins in corneas with and without stromal fibrosis: Delayed regeneration of apical epithelial growth factor barrier and the epithelial basement membrane in corneas with stromal fibrosis","volume":"202","author":"Tye","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_72","first-page":"565","article-title":"Role of transforming growth factor Beta in corneal function, biology and pathology","volume":"10","author":"Tandon","year":"2010","journal-title":"Curr. Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1167\/iovs.02-1188","article-title":"Molecular mechanisms controlling the fibrotic repair phenotype in cornea: Implications for surgical outcomes","volume":"44","author":"Stramer","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1097\/00055735-200108000-00001","article-title":"Extracellular matrix and wound healing","volume":"12","author":"Zieske","year":"2001","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_75","first-page":"703","article-title":"RNA interference targeting transforming growth factor-beta type II receptor suppresses ocular inflammation and fibrosis","volume":"10","author":"Nakamura","year":"2004","journal-title":"Mol. Vis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-immunol-032713-120257","article-title":"TGF-beta activation and function in immunity","volume":"32","author":"Travis","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Bayati, F., Mohammadi, M., Valadi, M., Jamshidi, S., Foma, A.M., and Sharif-Paghaleh, E. (2020). The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.585819"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Yang, Y., Wang, Z., Yang, H., Wang, L., Gillespie, S.R., Wolosin, J.M., Bernstein, A.M., and Reinach, P.S. (2013). TRPV1 potentiates TGFbeta-induction of corneal myofibroblast development through an oxidative stress-mediated p38-SMAD2 signaling loop. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077300"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/ni0606-557","article-title":"TGF-beta, a \u2018double agent\u2019 in the immune pathology war","volume":"7","author":"Cua","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_80","first-page":"313","article-title":"Enhancement of human neutrophil survival and activation by TGF-beta 1","volume":"43","author":"Lagraoui","year":"1997","journal-title":"Cell. Mol. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1111\/j.1471-4159.2009.06222.x","article-title":"Bioactive TGF-beta can associate with lipoproteins and is enriched in those containing apolipoprotein E3","volume":"110","author":"Tesseur","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/nm1095-1067","article-title":"Tamoxifen elevates transforming growth factor-beta and suppresses diet-induced formation of lipid lesions in mouse aorta","volume":"1","author":"Grainger","year":"1995","journal-title":"Nat. Med."},{"key":"ref_83","first-page":"1997","article-title":"Heparan sulfate deficiency leads to Peters anomaly in mice by disturbing neural crest TGF-beta2 signaling","volume":"119","author":"Iwao","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0888-7543(03)00046-6","article-title":"Molecular characterization of a familial translocation implicates disruption of HDAC9 and possible position effect on TGFbeta2 in the pathogenesis of Peters\u2019 anomaly","volume":"81","author":"David","year":"2003","journal-title":"Genomics"},{"key":"ref_85","first-page":"1942","article-title":"Anterior segment dysgenesis after overexpression of transforming growth factor-beta-induced gene, beta igh3, in the mouse eye","volume":"13","author":"Kim","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_86","unstructured":"Jat, N.S., and Tripathy, K. (2024). Peters Anomaly. StatPearls, StatPearls."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/s41431-019-0423-4","article-title":"Variable expressivity of syndromic BMP4-related eye, brain, and digital anomalies: A review of the literature and description of three new cases","volume":"27","author":"Blackburn","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_88","first-page":"577","article-title":"Keratoconus in vitro and the key players of the TGF-beta pathway","volume":"21","author":"Priyadarsini","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/13816810.2021.2015788","article-title":"A novel variant in TGFBI causes keratoconus in a two-generation Chinese family","volume":"43","author":"Lin","year":"2022","journal-title":"Ophthalmic Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/07853890701753664","article-title":"Stevens-Johnson syndrome: Pathogenesis, diagnosis, and management","volume":"40","author":"Hazin","year":"2008","journal-title":"Ann. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/j.1398-9995.2006.01295.x","article-title":"Ocular manifestations and complications of Stevens-Johnson syndrome and toxic epidermal necrolysis: An Asian series","volume":"62","author":"Yip","year":"2007","journal-title":"Allergy"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1136\/bjophthalmol-2017-310373","article-title":"Ocular surface cytokine profile in chronic Stevens-Johnson syndrome and its response to mucous membrane grafting for lid margin keratinisation","volume":"102","author":"Gurumurthy","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/mt.2009.263","article-title":"Pretranscriptional regulation of Tgf-beta1 by PI polyamide prevents scarring and accelerates wound healing of the cornea after exposure to alkali","volume":"18","author":"Chen","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s13346-018-0546-0","article-title":"Corneal chemical burn treatment through a delivery system consisting of TGF-beta(1) siRNA: In vitro and in vivo","volume":"8","author":"Soleimani","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.stemcr.2013.12.014","article-title":"Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells","volume":"2","author":"Mikhailova","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.exer.2019.03.014","article-title":"Expansion and maintenance of primary corneal epithelial stem\/progenitor cells by inhibition of TGFbeta receptor I-mediated signaling","volume":"182","author":"Hu","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/IIO.0000000000000112","article-title":"Corneal Haze Following Refractive Surgery: A Review of Pathophysiology, Incidence, Prevention, and Treatment","volume":"56","author":"Margo","year":"2016","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.exer.2012.03.018","article-title":"Corneal myofibroblast biology and pathobiology: Generation, persistence, and transparency","volume":"99","author":"Wilson","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1242\/jcs.112.5.613","article-title":"The cellular basis of corneal transparency: Evidence for \u2018corneal crystallins\u2019","volume":"112","author":"Jester","year":"1999","journal-title":"J. Cell Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/S0886-3350(01)01141-5","article-title":"Relation between corneal haze and transforming growth factor-beta1 after photorefractive keratectomy and laser in situ keratomileusis","volume":"27","author":"Kaji","year":"2001","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1076\/ceyr.16.1.19.5119","article-title":"Release of TGF-beta 1 and VEGF in tears following photorefractive keratectomy","volume":"16","author":"Vesaluoma","year":"1997","journal-title":"Curr. Eye Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3928\/1081-597X-20020301-05","article-title":"Comparison of TGF-beta1 in tears following laser subepithelial keratomileusis and photorefractive keratectomy","volume":"18","author":"Lee","year":"2002","journal-title":"J. Refract. Surg."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"708","DOI":"10.3928\/1081-597X-20060901-13","article-title":"Correlation between TGF-beta1 in tears and corneal haze following LASEK and epi-LASIK","volume":"22","author":"Long","year":"2006","journal-title":"J. Refract. Surg."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/S0886-3350(00)00625-8","article-title":"Mytomycin-C for post-PRK corneal haze","volume":"26","author":"Raviv","year":"2000","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"562","DOI":"10.3928\/1081-597X-20060601-08","article-title":"Effect of prophylactic and therapeutic mitomycin C on corneal apoptosis, cellular proliferation, haze, and long-term keratocyte density in rabbits","volume":"22","author":"Netto","year":"2006","journal-title":"J. Refract. Surg."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ajo.2011.05.034","article-title":"Keratocyte density 3 months, 15 months, and 3 years after corneal surface ablation with mitomycin C","volume":"153","author":"Canadas","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1080\/02713689808951251","article-title":"Neutralizing antibody to TGFbeta modulates stromal fibrosis but not regression of photoablative effect following PRK","volume":"17","author":"Cavanagh","year":"1998","journal-title":"Curr. Eye Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1167\/iovs.08-2919","article-title":"Trichostatin a inhibits corneal haze in vitro and in vivo","volume":"50","author":"Sharma","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jcrs.2009.07.042","article-title":"Inhibition of transforming growth factor-beta1 and its effects on human corneal fibroblasts by mannose-6-phosphate Potential for preventing haze after refractive surgery","volume":"36","author":"Angunawela","year":"2010","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Morris, J.C., Tan, A.R., Olencki, T.E., Shapiro, G.I., Dezube, B.J., Reiss, M., Hsu, F.J., Berzofsky, J.A., and Lawrence, D.P. (2014). Phase I study of GC1008 (fresolimumab): A human anti-transforming growth factor-beta (TGFbeta) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090353"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9028","DOI":"10.1200\/jco.2008.26.15_suppl.9028","article-title":"Phase I\/II study of GC1008: A human anti-transforming growth factor-beta (TGF\u03b2) monoclonal antibody (MAb) in patients with advanced malignant melanoma (MM) or renal cell carcinoma (RCC)","volume":"26","author":"Morris","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1002\/pro.2548","article-title":"Structures of a pan-specific antagonist antibody complexed to different isoforms of TGFbeta reveal structural plasticity of antibody-antigen interactions","volume":"23","author":"Moulin","year":"2014","journal-title":"Protein Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1200\/JCO.2021.39.15_suppl.2509","article-title":"Phase Ib study of the anti-TGF-\u03b2 monoclonal antibody (mAb) NIS793 combined with spartalizumab (PDR001), a PD-1 inhibitor, in patients (pts) with advanced solid tumors","volume":"39","author":"Bauer","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1200\/JCO.21.02229","article-title":"Long-Term Outcomes with Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients with Advanced Melanoma","volume":"40","author":"Wolchok","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6659","DOI":"10.18632\/oncotarget.23795","article-title":"Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class transforming growth factor-beta receptor type I inhibitor","volume":"9","author":"Yingling","year":"2018","journal-title":"Oncotarget"},{"key":"ref_116","first-page":"4479","article-title":"Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway","volume":"9","author":"Herbertz","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s13402-014-0210-8","article-title":"Anti-tumor activity of the TGF-beta receptor kinase inhibitor galunisertib (LY2157299 monohydrate) in patient-derived tumor xenografts","volume":"38","author":"Maier","year":"2015","journal-title":"Cell Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Peterson, J.M., Jay, J.W., Wang, Y., Joglar, A.A., Prasai, A., Palackic, A., Wolf, S.E., and El Ayadi, A. (2022). Galunisertib Exerts Antifibrotic Effects on TGF-beta-Induced Fibroproliferative Dermal Fibroblasts. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126689"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40425-018-0356-4","article-title":"Targeting the TGFbeta pathway with galunisertib, a TGFbetaRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade","volume":"6","author":"Holmgaard","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"21614","DOI":"10.18632\/oncotarget.4308","article-title":"Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients","volume":"6","author":"Serova","year":"2015","journal-title":"Oncotarget"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/ardp.201400116","article-title":"Targeting the TGF-beta receptor with kinase inhibitors for scleroderma therapy","volume":"347","author":"Cong","year":"2014","journal-title":"Arch. Pharm."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1600-0625.2011.01419.x","article-title":"Local injection of latency-associated peptide, a linker propeptide specific for active form of transforming growth factor-beta1, inhibits dermal sclerosis in bleomycin-induced murine scleroderma","volume":"21","author":"Oyama","year":"2012","journal-title":"Exp. Dermatol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.4049\/jimmunol.163.10.5693","article-title":"Anti-TGF-\u03b2 Treatment Prevents Skin and Lung Fibrosis in Murine Sclerodermatous Graft-Versus-Host Disease: A Model for Human Scleroderma","volume":"163","author":"McCormick","year":"1999","journal-title":"J. Immunol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.cellsig.2008.01.006","article-title":"Targeting the TGFbeta, endothelin-1 and CCN2 axis to combat fibrosis in scleroderma","volume":"20","author":"Leask","year":"2008","journal-title":"Cell Signal"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1253\/circj.CJ-13-0183","article-title":"Targeting transforming growth factor-beta signaling in aortopathies in Marfan syndrome","volume":"77","author":"Sawaki","year":"2013","journal-title":"Circ. J."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1126\/science.1192149","article-title":"Noncanonical TGFbeta signaling contributes to aortic aneurysm progression in Marfan syndrome mice","volume":"332","author":"Holm","year":"2011","journal-title":"Science"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.bbadis.2017.11.015","article-title":"Altered TGF-beta endocytic trafficking contributes to the increased signaling in Marfan syndrome","volume":"1864","author":"Siegert","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"227","DOI":"10.5603\/CJ.2013.0066","article-title":"The role of transforming growth factor-beta in Marfan syndrome","volume":"20","author":"Benke","year":"2013","journal-title":"Cardiol. J."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Shi, X., Young, C.D., Zhou, H., and Wang, X. (2020). Transforming Growth Factor-beta Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts. Biomolecules, 10.","DOI":"10.3390\/biom10121666"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4093\/dmj.2022.0231","article-title":"Alantolactone Attenuates Renal Fibrosis via Inhibition of Transforming Growth Factor beta\/Smad3 Signaling Pathway","volume":"48","author":"Lee","year":"2024","journal-title":"Diabetes Metab. J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1093\/neuonc\/noq142","article-title":"Targeted therapy for high-grade glioma with the TGF-beta2 inhibitor trabedersen: Results of a randomized and controlled phase IIb study","volume":"13","author":"Bogdahn","year":"2011","journal-title":"Neuro Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"ehab724.1554","DOI":"10.1093\/eurheartj\/ehab724.1554","article-title":"Angiotensin II receptor blockers in modulation of transforming growth factor-beta effects on mitral valve myxomatous degeneration","volume":"42","author":"Malev","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_133","unstructured":"Anna Naidenova, T. (2017). Signaling Pathways of Cardiac Remodeling Related to Angiotensin II. Renin-Angiotensin System, IntechOpen. Chapter 4."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1182\/blood.V126.23.1669.1669","article-title":"Phase 2 Study of Monotherapy Galunisertib (LY2157299 Monohydrate) in Very Low-, Low-, and Intermediate-Risk Patients with Myelodysplastic Syndromes","volume":"126","author":"Valcarcel","year":"2015","journal-title":"Blood"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3109\/08977194.2011.595411","article-title":"Exploring anti-TGF-beta therapies in cancer and fibrosis","volume":"29","author":"Hawinkels","year":"2011","journal-title":"Growth Factors"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Lebrun, J.J. (2012). The Dual Role of TGFbeta in Human Cancer: From Tumor Suppression to Cancer Metastasis. ISRN Mol. Biol., 2012.","DOI":"10.5402\/2012\/381428"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00262-015-1653-0","article-title":"Cutaneous keratoacanthomas\/squamous cell carcinomas associated with neutralization of transforming growth factor beta by the monoclonal antibody fresolimumab (GC1008)","volume":"64","author":"Lacouture","year":"2015","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/nrrheum.2009.26","article-title":"Transforming growth factor beta as a therapeutic target in systemic sclerosis","volume":"5","author":"Varga","year":"2009","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.ekir.2017.03.011","article-title":"A Phase 2, Double-Blind, Placebo-Controlled, Randomized Study of Fresolimumab in Patients with Steroid-Resistant Primary Focal Segmental Glomerulosclerosis","volume":"2","author":"Vincenti","year":"2017","journal-title":"Kidney Int. Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/nrd.2017.225","article-title":"Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease","volume":"16","author":"Mora","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jneuroim.2016.01.014","article-title":"Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice","volume":"292","author":"Sun","year":"2016","journal-title":"J. Neuroimmunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1167\/iovs.02-0978","article-title":"Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery","volume":"44","author":"Mead","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_143","first-page":"2301","article-title":"TGF-beta2-induced matrix modification and cell transdifferentiation in the human lens capsular bag","volume":"43","author":"Wormstone","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Liu, Y., Paauwe, M., Nixon, A.B., and Hawinkels, L. (2020). Endoglin Targeting: Lessons Learned and Questions That Remain. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010147"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13045-021-01053-x","article-title":"Novel therapies emerging in oncology to target the TGF-beta pathway","volume":"14","author":"Kim","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.1158\/1078-0432.CCR-23-0276","article-title":"A Phase Ib Trial of AVID200, a TGFbeta 1\/3 Trap, in Patients with Myelofibrosis","volume":"29","author":"Mascarenhas","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e145651","DOI":"10.1172\/jci.insight.145651","article-title":"TGF-beta1 protein trap AVID200 beneficially affects hematopoiesis and bone marrow fibrosis in myelofibrosis","volume":"6","author":"Varricchio","year":"2021","journal-title":"JCI Insight"},{"key":"ref_148","first-page":"A6","article-title":"P855\u2005High-resolution maps of heterogeneous antigen expression in glioblastoma and implications for immunotherapy","volume":"8","author":"Barish","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Hanafy, N.A.N., Fabregat, I., Leporatti, S., and Kemary, M.E. (2020). Encapsulating TGF-beta1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12050421"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1039\/c0mb00115e","article-title":"Peptide ligands that use a novel binding site to target both TGF-beta receptors","volume":"6","author":"Li","year":"2010","journal-title":"Mol. Biosyst."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"17754","DOI":"10.1021\/bi981931e","article-title":"Novel peptides selected to bind vascular endothelial growth factor target the receptor-binding site","volume":"37","author":"Fairbrother","year":"1998","journal-title":"Biochemistry"},{"key":"ref_152","first-page":"4196","article-title":"Shared and Tissue-Specific Genetic Features of Primary Myelofibrosis, Hepatic Fibrosis, Idiopathic Pulmonary Fibrosis and Kidney Fibrosis","volume":"130","author":"Dohlman","year":"2017","journal-title":"Blood"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/ijc.11494","article-title":"Expression of TGF-beta type II receptor antisense RNA impairs TGF-beta signaling in vitro and promotes mammary gland differentiation in vivo","volume":"107","author":"Lenferink","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.1038\/mtna.2014.7","article-title":"Targeting TGF-beta Signaling by Antisense Oligonucleotide-mediated Knockdown of TGF-beta Type I Receptor","volume":"3","author":"Kemaladewi","year":"2014","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Dai, H., Abdullah, R., Wu, X., Li, F., Ma, Y., Lu, A., and Zhang, G. (2022). Pancreatic Cancer: Nucleic Acid Drug Discovery and Targeted Therapy. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.855474"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.gde.2005.12.009","article-title":"Inhibition of TGFbeta signaling in cancer therapy","volume":"16","author":"Arteaga","year":"2006","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Kuespert, S., Heydn, R., Peters, S., Wirkert, E., Meyer, A.L., Sieborger, M., Johannesen, S., Aigner, L., Bogdahn, U., and Bruun, T.H. (2020). Antisense Oligonucleotide in LNA-Gapmer Design Targeting TGFBR2-A Key Single Gene Target for Safe and Effective Inhibition of TGFbeta Signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061952"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"317068","DOI":"10.1155\/2010\/317068","article-title":"Tgf-Beta superfamily receptors-targets for antiangiogenic therapy?","volume":"2010","author":"Otten","year":"2010","journal-title":"J. Oncol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0378-1119(94)90408-1","article-title":"Antisense oligodeoxyribonucleotide inhibition of TGF-beta 1 gene expression and alterations in the growth and malignant properties of mouse fibrosarcoma cells","volume":"149","author":"Spearman","year":"1994","journal-title":"Gene"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1210\/endo.138.11.5475","article-title":"Endoglin regulates trophoblast differentiation along the invasive pathway in human placental villous explants","volume":"138","author":"Caniggia","year":"1997","journal-title":"Endocrinology"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1093\/neuonc\/nor046","article-title":"Trabedersen to target transforming growth factor-\u03b2: When the journey is not the reward, in reference to Bogdahn et al. (Neuro-Oncology 2011;13:132\u2013142)","volume":"13","author":"Wick","year":"2011","journal-title":"Neuro Oncol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Bara\u0144ska, J. (2020). Recent Advances in Understanding Mechanisms of TGF Beta Signaling and Its Role in Glioma Pathogenesis. Glioma Signaling, Springer International Publishing.","DOI":"10.1007\/978-3-030-30651-9"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1186\/s13287-021-02524-1","article-title":"Mesenchymal stem cell-derived extracellular vesicles in therapy against fibrotic diseases","volume":"12","author":"Huang","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1158\/1535-7163.737.3.6","article-title":"SB-431542, a small molecule transforming growth factor-beta-receptor antagonist, inhibits human glioma cell line proliferation and motility","volume":"3","author":"Hjelmeland","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1158\/0008-5472.CAN-11-1212","article-title":"Blockade of TGF-beta signaling by the TGFbetaR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma","volume":"71","author":"Zhang","year":"2011","journal-title":"Cancer Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"109884","DOI":"10.1016\/j.exer.2024.109884","article-title":"Two-phase mechanism in the treatment of corneal stromal fibrosis with topical losartan","volume":"242","author":"Wilson","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"18842","DOI":"10.1074\/jbc.M700243200","article-title":"A novel modulatory mechanism of transforming growth factor-beta signaling through decorin and LRP-1","volume":"282","author":"Brandan","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"108933","DOI":"10.1016\/j.exer.2022.108933","article-title":"Decorin regulates collagen fibrillogenesis during corneal wound healing in mouse in vivo","volume":"216","author":"Gupta","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1167\/iovs.11-7357","article-title":"Significant inhibition of corneal scarring in vivo with tissue-selective, targeted AAV5 decorin gene therapy","volume":"52","author":"Mohan","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"110","DOI":"10.2174\/156652411794859241","article-title":"Decorin biology, expression, function and therapy in the cornea","volume":"11","author":"Mohan","year":"2011","journal-title":"Curr. Mol. Med."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Chou, Y.F., Lan, Y.H., Hsiao, J.H., Chen, C.Y., Chou, P.Y., and Sheu, M.J. (2022). Curcuminoids Inhibit Angiogenic Behaviors of Human Umbilical Vein Endothelial Cells via Endoglin\/Smad1 Signaling. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073889"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s43162-021-00056-x","article-title":"Antiangiogenic role of natural flavonoids and their molecular mechanism: An update","volume":"33","author":"Subbaraj","year":"2021","journal-title":"Egypt. J. Intern. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/00003226-199703000-00010","article-title":"Inhibition of corneal fibrosis by topical application of blocking antibodies to TGF beta in the rabbit","volume":"16","author":"Jester","year":"1997","journal-title":"Cornea"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12943-022-01569-x","article-title":"Targeting TGF-beta signal transduction for fibrosis and cancer therapy","volume":"21","author":"Peng","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1200\/JCO.2007.11.8984","article-title":"Biology of interactions: Antiepidermal growth factor receptor agents","volume":"25","author":"Harari","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/jcb.240410306","article-title":"Modulation of transforming growth factor alpha-dependent expression of epidermal growth factor receptor gene by transforming growth factor beta, triiodothyronine, and retinoic acid","volume":"41","author":"Klos","year":"1989","journal-title":"J. Cell Biochem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1038\/sj.onc.1206617","article-title":"Inhibition of the antiproliferative effect of TGFbeta by EGF in primary human ovarian cancer cells","volume":"22","author":"Dunfield","year":"2003","journal-title":"Oncogene"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.yexcr.2005.07.023","article-title":"Modulation of TGF-beta signaling by EGF-CFC proteins","volume":"310","author":"Wechselberger","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"C1231","DOI":"10.1152\/ajpcell.00040.2022","article-title":"Platelets and tyrosine kinase inhibitors: Clinical features, mechanisms of action, and effects on physiology","volume":"323","author":"Zheng","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12943-018-0793-1","article-title":"EGFR-TKIs resistance via EGFR-independent signaling pathways","volume":"17","author":"Liu","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.bcp.2008.05.024","article-title":"Erlotinib and gefitinib for the treatment of myelodysplastic syndrome and acute myeloid leukemia: A preclinical comparison","volume":"76","author":"Boehrer","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"8079","DOI":"10.1038\/s41598-019-42969-2","article-title":"Epidermal Growth Factor Stimulates Transforming Growth Factor-Beta Receptor Type II Expression In Corneal Epithelial Cells","volume":"9","author":"Shu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00417-021-05370-2","article-title":"Lobeglitazone attenuates fibrosis in corneal fibroblasts by interrupting TGF-beta-mediated Smad signaling","volume":"260","author":"Nuwormegbe","year":"2022","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1186\/s12931-022-02285-2","article-title":"Amphiregulin induces CCN2 and fibronectin expression by TGF-beta through EGFR-dependent pathway in lung epithelial cells","volume":"23","author":"Cheng","year":"2022","journal-title":"Respir. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14756366.2017.1370583","article-title":"Discovery of novel dual inhibitors of receptor tyrosine kinases EGFR and PDGFR-beta related to anticancer drug resistance","volume":"33","author":"Fischer","year":"2018","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.1021\/acs.jmedchem.1c01714","article-title":"Development of Dual Inhibitors Targeting Epidermal Growth Factor Receptor in Cancer Therapy","volume":"65","author":"Tan","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_188","first-page":"3000","article-title":"Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer","volume":"119","author":"Regales","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ejmech.2017.07.023","article-title":"How to train your inhibitor: Design strategies to overcome resistance to Epidermal Growth Factor Receptor inhibitors","volume":"142","author":"Milik","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/j.1349-7006.2005.00103.x","article-title":"The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-beta","volume":"96","author":"Tojo","year":"2005","journal-title":"Cancer Sci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.exer.2015.10.021","article-title":"Inhibition of TGFbeta cell signaling for limbal explant culture in serumless, defined xeno-free conditions","volume":"145","author":"Zamudio","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Aouimeur, I., Sagnial, T., Coulomb, L., Maurin, C., Thomas, J., Forestier, P., Ninotta, S., Perrache, C., Forest, F., and Gain, P. (2023). Investigating the Role of TGF-beta Signaling Pathways in Human Corneal Endothelial Cell Primary Culture. Cells, 12.","DOI":"10.3390\/cells12121624"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/13\/1105\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:04:38Z","timestamp":1760108678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/13\/1105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":192,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["cells13131105"],"URL":"https:\/\/doi.org\/10.3390\/cells13131105","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,26]]}}}