{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:42:25Z","timestamp":1784691745463,"version":"3.55.0"},"reference-count":134,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-25216-9","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T11:24:39Z","timestamp":1763724279000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cannabidiol inhibits TGF-\u03b21-induced epithelial-mesenchymal transition in human conjunctival epithelial cells by interrupting TGF-\u03b2\/Smad signaling"],"prefix":"10.1038","volume":"15","author":[{"given":"Anil","family":"Baskan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezzat M.","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ava","family":"Elahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javeria","family":"Pervaiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talin","family":"Barisani-Asenbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"25216_CR1","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","volume":"587","author":"NC Henderson","year":"2020","unstructured":"Henderson, N. C., Rieder, F. & Wynn, T. A. Fibrosis: From mechanisms to medicines. Nature 587, 555\u2013566 (2020).","journal-title":"Nature"},{"key":"25216_CR2","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.exer.2015.03.021","volume":"142","author":"G Schlunck","year":"2016","unstructured":"Schlunck, G., Meyer-ter-Vehn, T., Klink, T. & Grehn, F. Conjunctival fibrosis following filtering glaucoma surgery. Exp. Eye Res. 142, 76\u201382 (2016).","journal-title":"Exp. Eye Res."},{"key":"25216_CR3","doi-asserted-by":"publisher","first-page":"4004","DOI":"10.3390\/ijms24044004","volume":"24","author":"SA Antar","year":"2023","unstructured":"Antar, S. A., Ashour, N. A., Marawan, M. E. & Al-Karmalawy, A. A. Fibrosis: Types, effects, markers, mechanisms for disease progression, and its relation with oxidative stress, immunity, and inflammation. Int. J. Mol. Sci. 24, 4004 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"25216_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108047","volume":"197","author":"J Raji\u0107","year":"2020","unstructured":"Raji\u0107, J. et al. DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells. Exp. Eye Res. 197, 108047 (2020).","journal-title":"Exp. Eye Res."},{"key":"25216_CR5","doi-asserted-by":"publisher","first-page":"3852","DOI":"10.1016\/j.cell.2021.06.024","volume":"184","author":"MV Plikus","year":"2021","unstructured":"Plikus, M. V. et al. Fibroblasts: Origins, definitions, and functions in health and disease. Cell 184, 3852\u20133872 (2021).","journal-title":"Cell"},{"key":"25216_CR6","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.3390\/cells10071587","volume":"10","author":"GD Marconi","year":"2021","unstructured":"Marconi, G. D. et al. Epithelial-Mesenchymal Transition (EMT): The Type-2 EMT in wound healing, tissue regeneration and organ fibrosis. Cells 10, 1587 (2021).","journal-title":"Cells"},{"key":"25216_CR7","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","volume":"139","author":"JP Thiery","year":"2009","unstructured":"Thiery, J. P., Acloque, H., Huang, R. Y. J. & Nieto, M. A. Epithelial-mesenchymal transitions in development and disease. Cell 139, 871\u2013890 (2009).","journal-title":"Cell"},{"key":"25216_CR8","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00441-016-2464-0","volume":"365","author":"RC Stone","year":"2016","unstructured":"Stone, R. C. et al. Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res. 365, 495\u2013506 (2016).","journal-title":"Cell Tissue Res."},{"key":"25216_CR9","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s00441-011-1227-1","volume":"347","author":"RM Carew","year":"2012","unstructured":"Carew, R. M., Wang, B. & Kantharidis, P. The role of EMT in renal fibrosis. Cell Tissue Res. 347, 103\u2013116 (2012).","journal-title":"Cell Tissue Res."},{"key":"25216_CR10","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.devcel.2021.02.028","volume":"56","author":"Y Katsuno","year":"2021","unstructured":"Katsuno, Y. & Derynck, R. Epithelial plasticity, epithelial-mesenchymal transition, and the TGF-\u03b2 family. Dev. Cell 56, 726\u2013746 (2021).","journal-title":"Dev. Cell"},{"key":"25216_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108594","volume":"207","author":"SE Wilson","year":"2021","unstructured":"Wilson, S. E. TGF beta \u22121, \u22122 and \u22123 in the modulation of fibrosis in the cornea and other organs. Exp. Eye Res. 207, 108594 (2021).","journal-title":"Exp. Eye Res."},{"key":"25216_CR12","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1038\/onc.2013.128","volume":"33","author":"H Zheng","year":"2014","unstructured":"Zheng, H. & Kang, Y. Multilayer control of the EMT master regulators. Oncogene 33, 1755\u20131763 (2014).","journal-title":"Oncogene"},{"key":"25216_CR13","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1172\/JCI0215518","volume":"110","author":"M Iwano","year":"2002","unstructured":"Iwano, M. et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J. Clin. Invest. 110, 341\u2013350 (2002).","journal-title":"J. Clin. Invest."},{"key":"25216_CR14","doi-asserted-by":"publisher","first-page":"13180","DOI":"10.1073\/pnas.0605669103","volume":"103","author":"KK Kim","year":"2006","unstructured":"Kim, K. K. et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc. Natl. Acad. Sci. 103, 13180\u201313185 (2006).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"25216_CR15","doi-asserted-by":"publisher","first-page":"23337","DOI":"10.1074\/jbc.M700194200","volume":"282","author":"M Zeisberg","year":"2007","unstructured":"Zeisberg, M. et al. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition*. J. Biol. Chem. 282, 23337\u201323347 (2007).","journal-title":"J. Biol. Chem."},{"key":"25216_CR16","doi-asserted-by":"publisher","first-page":"20202","DOI":"10.1074\/jbc.M110.102012","volume":"285","author":"SN Flier","year":"2010","unstructured":"Flier, S. N. et al. Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis*. J. Biol. Chem. 285, 20202\u201320212 (2010).","journal-title":"J. Biol. Chem."},{"key":"25216_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0278158","volume":"17","author":"X Hu","year":"2022","unstructured":"Hu, X. et al. MiR-302d inhibits TGFB-induced EMT and promotes MET in primary human RPE cells. PLoS ONE 17, e0278158 (2022).","journal-title":"PLoS ONE"},{"key":"25216_CR18","doi-asserted-by":"publisher","first-page":"11842","DOI":"10.1038\/s41598-021-90618-4","volume":"11","author":"Y Kobayashi","year":"2021","unstructured":"Kobayashi, Y. et al. Inhibition of epithelial\u2013mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-\u03b1 agonist. Sci. Rep. 11, 11842 (2021).","journal-title":"Sci. Rep."},{"key":"25216_CR19","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jare.2023.06.004","volume":"60","author":"Y-C Yang","year":"2024","unstructured":"Yang, Y.-C. et al. Inhibition of oxidative stress-induced epithelial-mesenchymal transition in retinal pigment epithelial cells of age-related macular degeneration model by suppressing ERK activation. J. Adv. Res. 60, 141\u2013157 (2024).","journal-title":"J. Adv. Res."},{"key":"25216_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41419-023-05693-4","volume":"14","author":"X Ma","year":"2023","unstructured":"Ma, X. et al. DAPL1 prevents epithelial\u2013mesenchymal transition in the retinal pigment epithelium and experimental proliferative vitreoretinopathy. Cell Death Dis. 14, 1\u201312 (2023).","journal-title":"Cell Death Dis."},{"key":"25216_CR21","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.stemcr.2020.03.009","volume":"14","author":"NC Boles","year":"2020","unstructured":"Boles, N. C. et al. Epigenomic and transcriptomic changes during human RPE EMT in a stem cell model of epiretinal membrane pathogenesis and prevention by nicotinamide. Stem Cell Rep. 14, 631\u2013647 (2020).","journal-title":"Stem Cell Rep."},{"key":"25216_CR22","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1007\/s12013-024-01305-w","volume":"82","author":"Y Mysore","year":"2024","unstructured":"Mysore, Y. et al. Epithelial-mesenchymal transition (EMT) and the effect of atorvastatin on it in ARPE-19 cells. Cell Biochem. Biophys. 82, 1523\u20131536 (2024).","journal-title":"Cell Biochem. Biophys."},{"key":"25216_CR23","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.3390\/ijms21124271","volume":"21","author":"DY Shu","year":"2020","unstructured":"Shu, D. Y., Butcher, E. & Saint-Geniez, M. EMT and EndMT: emerging roles in age-related macular degeneration. Int. J. Mol. Sci. 21, 4271 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"25216_CR24","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1167\/iovs.06-1060","volume":"48","author":"N Kato","year":"2007","unstructured":"Kato, N. et al. \u03b2-Catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium. Investig. Opthalmology Vis. Sci. 48, 1511 (2007).","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"25216_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2022.102936","volume":"64","author":"M Domdey","year":"2022","unstructured":"Domdey, M. et al. Consecutive dosing of UVB irradiation induces loss of ABCB5 expression and activation of EMT and fibrosis proteins in limbal epithelial cells similar to pterygium epithelium. Stem Cell Res. 64, 102936 (2022).","journal-title":"Stem Cell Res."},{"key":"25216_CR26","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1002\/1873-3468.13698","volume":"594","author":"X Zhong","year":"2020","unstructured":"Zhong, X. et al. MiR-3175 promotes epithelial-mesenchymal transition by targeting Smad7 in human conjunctiva and pterygium. FEBS Lett. 594, 1207\u20131217 (2020).","journal-title":"FEBS Lett."},{"key":"25216_CR27","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.mucimm.2023.11.008","volume":"17","author":"Z Liu","year":"2024","unstructured":"Liu, Z. et al. Single-cell landscape reveals the epithelial cell-centric pro-inflammatory immune microenvironment in dry eye development. Mucosal Immunol. 17, 491\u2013507 (2024).","journal-title":"Mucosal Immunol."},{"key":"25216_CR28","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.2353\/ajpath.2009.090318","volume":"175","author":"Y Ogawa","year":"2009","unstructured":"Ogawa, Y. et al. Epithelial mesenchymal transition in human ocular chronic graft-versus-host disease. Am. J. Pathol. 175, 2372\u20132381 (2009).","journal-title":"Am. J. Pathol."},{"key":"25216_CR29","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3389\/fcimb.2017.00253","volume":"7","author":"J Raji\u0107","year":"2017","unstructured":"Raji\u0107, J. et al. Chlamydia trachomatis infection is associated with E-Cadherin promoter methylation, downregulation of E-cadherin expression, and increased expression of fibronectin and \u03b1-SMA\u2014implications for epithelial-mesenchymal transition. Front. Cell. Infect. Microbiol. 7, 253 (2017).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"25216_CR30","doi-asserted-by":"publisher","first-page":"101301","DOI":"10.1016\/j.isci.2020.101301","volume":"23","author":"F Shahbazi","year":"2020","unstructured":"Shahbazi, F., Grandi, V., Banerjee, A. & Trant, J. F. Cannabinoids and cannabinoid receptors: The story so far. IScience 23, 101301 (2020).","journal-title":"IScience"},{"key":"25216_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.33594\/000000371","volume":"55","author":"A Aebersold","year":"2021","unstructured":"Aebersold, A., Duff, M., Sloan, L. & Song, Z.-H. Cannabidiol signaling in the eye and its potential as an ocular therapeutic agent. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 55, 1\u201314 (2021).","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"25216_CR32","doi-asserted-by":"publisher","first-page":"473","DOI":"10.3390\/molecules29020473","volume":"29","author":"N Martinez Naya","year":"2024","unstructured":"Martinez Naya, N. et al. An overview of cannabidiol as a multifunctional drug: Pharmacokinetics and cellular effects. Molecules 29, 473 (2024).","journal-title":"Molecules"},{"key":"25216_CR33","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.3390\/molecules28073271","volume":"28","author":"J Castillo-Arellano","year":"2023","unstructured":"Castillo-Arellano, J., Canseco-Alba, A., Cutler, S. J. & Le\u00f3n, F. The polypharmacological effects of cannabidiol. Molecules 28, 3271 (2023).","journal-title":"Molecules"},{"key":"25216_CR34","doi-asserted-by":"publisher","first-page":"e170","DOI":"10.1038\/cddis.2011.52","volume":"2","author":"MP Lim","year":"2011","unstructured":"Lim, M. P., Devi, L. A. & Rozenfeld, R. Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death Dis. 2, e170\u2013e170 (2011).","journal-title":"Cell Death Dis."},{"key":"25216_CR35","doi-asserted-by":"publisher","first-page":"166753","DOI":"10.1016\/j.bbadis.2023.166753","volume":"1869","author":"A Krzy\u017cewska","year":"2023","unstructured":"Krzy\u017cewska, A., Baranowska-Kuczko, M., Kasacka, I. & Koz\u0142owska, H. Cannabidiol alleviates right ventricular fibrosis by inhibiting the transforming growth factor \u03b2 pathway in monocrotaline-induced pulmonary hypertension in rats. Biochim. Biophys. Acta BBA \u2013 Mol. Basis Dis. 1869, 166753 (2023).","journal-title":"Biochim. Biophys. Acta BBA \u2013 Mol. Basis Dis."},{"key":"25216_CR36","doi-asserted-by":"publisher","first-page":"10141","DOI":"10.3389\/ebm.2024.10141","volume":"249","author":"R Ma","year":"2024","unstructured":"Ma, R. et al. Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-\u03baB and PPAR-\u03b1 pathways. Exp. Biol. Med. 249, 10141 (2024).","journal-title":"Exp. Biol. Med."},{"key":"25216_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.981817","volume":"13","author":"C del R\u00edo","year":"2022","unstructured":"del R\u00edo, C. et al. Cannabidiol markedly alleviates skin and liver fibrosis. Front. Pharmacol. 13, 981817 (2022).","journal-title":"Front. Pharmacol."},{"key":"25216_CR38","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1016\/j.jacc.2010.07.033","volume":"56","author":"M Rajesh","year":"2010","unstructured":"Rajesh, M. et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J. Am. Coll. Cardiol. 56, 2115\u20132125 (2010).","journal-title":"J. Am. Coll. Cardiol."},{"key":"25216_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113088","volume":"142","author":"W Shao","year":"2024","unstructured":"Shao, W. et al. Cannabidiol suppresses silica-induced pulmonary inflammation and fibrosis through regulating NLRP3\/TGF-\u03b21\/Smad2\/3 pathway. Int. Immunopharmacol. 142, 113088 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"25216_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.115374","volume":"263","author":"D Luo","year":"2023","unstructured":"Luo, D. et al. Cannabidiol alleviates perfluorooctane sulfonate-induced macrophage extracellular trap mediate inflammation and fibrosis in mice liver. Ecotoxicol. Environ. Saf. 263, 115374 (2023).","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"25216_CR41","doi-asserted-by":"publisher","first-page":"1358626","DOI":"10.3389\/fphar.2024.1358626","volume":"15","author":"M Sun","year":"2024","unstructured":"Sun, M. et al. Integrating fecal metabolomics and intestinal microbiota to study the mechanism of cannabidiol in the treatment of idiopathic pulmonary fibrosis. Front. Pharmacol. 15, 1358626 (2024).","journal-title":"Front. Pharmacol."},{"key":"25216_CR42","doi-asserted-by":"publisher","DOI":"10.1089\/can.2023.0285","author":"D Flores-Cortez","year":"2024","unstructured":"Flores-Cortez, D. et al. Hepatoprotective effect of cannabidiol on the progression of experimental hepatic cirrhosis in rats. Cannabis Cannabinoid Res. https:\/\/doi.org\/10.1089\/can.2023.0285 (2024).","journal-title":"Cannabis Cannabinoid Res."},{"key":"25216_CR43","doi-asserted-by":"publisher","first-page":"6341","DOI":"10.1038\/s41598-023-33507-2","volume":"13","author":"S Suzuki","year":"2023","unstructured":"Suzuki, S., Fleig, A. & Penner, R. CBGA ameliorates inflammation and fibrosis in nephropathy. Sci. Rep. 13, 6341 (2023).","journal-title":"Sci. Rep."},{"key":"25216_CR44","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.ejphar.2018.11.029","volume":"843","author":"F Vuolo","year":"2019","unstructured":"Vuolo, F. et al. Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma. Eur. J. Pharmacol. 843, 251\u2013259 (2019).","journal-title":"Eur. J. Pharmacol."},{"key":"25216_CR45","doi-asserted-by":"publisher","first-page":"6766","DOI":"10.3390\/ijms23126766","volume":"23","author":"L Mili\u00e1n","year":"2022","unstructured":"Mili\u00e1n, L. et al. In vitro effect of \u03949-Tetrahydrocannabinol and cannabidiol on cancer-associated fibroblasts isolated from lung cancer. Int. J. Mol. Sci. 23, 6766 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"25216_CR46","doi-asserted-by":"publisher","first-page":"e0228909","DOI":"10.1371\/journal.pone.0228909","volume":"15","author":"L Milian","year":"2020","unstructured":"Milian, L. et al. Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. PLoS ONE 15, e0228909 (2020).","journal-title":"PLoS ONE"},{"key":"25216_CR47","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.3390\/ijms21072429","volume":"21","author":"L Garc\u00eda-Morales","year":"2020","unstructured":"Garc\u00eda-Morales, L. et al. CBD reverts the mesenchymal invasive phenotype of breast cancer cells induced by the inflammatory cytokine IL-1\u03b2. Int. J. Mol. Sci. 21, 2429 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"25216_CR48","doi-asserted-by":"publisher","first-page":"13235","DOI":"10.3390\/ijms241713235","volume":"24","author":"L Garc\u00eda-Morales","year":"2023","unstructured":"Garc\u00eda-Morales, L., Mendoza-Rodr\u00edguez, M. G., Ram\u00edrez, J. T. & Meza, I. CBD inhibits in vivo development of human breast cancer tumors. Int. J. Mol. Sci. 24, 13235 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"25216_CR49","doi-asserted-by":"publisher","first-page":"3587","DOI":"10.1007\/s00432-022-04265-x","volume":"149","author":"P Feng","year":"2023","unstructured":"Feng, P. et al. Cannabidiol inhibits invasion and metastasis in colorectal cancer cells by reversing epithelial\u2013mesenchymal transition through the Wnt\/\u03b2-catenin signaling pathway. J. Cancer Res. Clin. Oncol. 149, 3587\u20133598 (2023).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"25216_CR50","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1186\/s12967-022-03773-1","volume":"20","author":"T Liu","year":"2022","unstructured":"Liu, T. et al. Discovery of a pyrano[2,3-b]pyridine derivative YX-2102 as a cannabinoid receptor 2 agonist for alleviating lung fibrosis. J. Transl. Med. 20, 565 (2022).","journal-title":"J. Transl. Med."},{"key":"25216_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167848","volume":"11","author":"T Yoshinaga","year":"2016","unstructured":"Yoshinaga, T. et al. AM251 suppresses epithelial-mesenchymal transition of renal tubular epithelial cells. PLoS ONE 11, e0167848 (2016).","journal-title":"PLoS ONE"},{"key":"25216_CR52","doi-asserted-by":"publisher","first-page":"607483","DOI":"10.3389\/fcell.2020.607483","volume":"8","author":"J Di Gregorio","year":"2020","unstructured":"Di Gregorio, J. et al. The epithelial-to-mesenchymal transition as a possible therapeutic target in fibrotic disorders. Front. Cell Dev. Biol. 8, 607483 (2020).","journal-title":"Front. Cell Dev. Biol."},{"key":"25216_CR53","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.3390\/pharmaceutics15041077","volume":"15","author":"SM Saraiva","year":"2023","unstructured":"Saraiva, S. M., Mart\u00edn-Banderas, L. & Dur\u00e1n-Lobato, M. Cannabinoid-Based ocular therapies and formulations. Pharmaceutics 15, 1077 (2023).","journal-title":"Pharmaceutics"},{"key":"25216_CR54","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.survophthal.2020.07.002","volume":"66","author":"MTM Wang","year":"2021","unstructured":"Wang, M. T. M. & Danesh-Meyer, H. V. Cannabinoids and the eye. Surv. Ophthalmol. 66, 327\u2013345 (2021).","journal-title":"Surv. Ophthalmol."},{"key":"25216_CR55","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1080\/09273948.2020.1726969","volume":"29","author":"AX Nguyen","year":"2021","unstructured":"Nguyen, A. X. & Wu, A. Y. Cannabis and the cornea. Ocul. Immunol. Inflamm. 29, 1023\u20131028 (2021).","journal-title":"Ocul. Immunol. Inflamm."},{"key":"25216_CR56","doi-asserted-by":"publisher","first-page":"2496","DOI":"10.1167\/iovs.02-0851","volume":"44","author":"IK Gipson","year":"2003","unstructured":"Gipson, I. K. et al. Mucin gene expression in immortalized human corneal-limbal and conjunctival epithelial cell lines. Investig. Opthalmology Vis. Sci. 44, 2496 (2003).","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"25216_CR57","doi-asserted-by":"publisher","first-page":"5157","DOI":"10.1128\/MCB.22.14.5157-5172.2002","volume":"22","author":"JG Rheinwald","year":"2002","unstructured":"Rheinwald, J. G. et al. A Two-Stage, p16INK4A- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status. Mol. Cell. Biol. 22, 5157\u20135172 (2002).","journal-title":"Mol. Cell. Biol."},{"key":"25216_CR58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087293","volume":"9","author":"A Degasperi","year":"2014","unstructured":"Degasperi, A. et al. Evaluating strategies to normalise biological replicates of western blot data. PLoS ONE 9, e87293 (2014).","journal-title":"PLoS ONE"},{"key":"25216_CR59","doi-asserted-by":"publisher","first-page":"196","DOI":"10.3109\/08977194.2011.595714","volume":"29","author":"A Biernacka","year":"2011","unstructured":"Biernacka, A., Dobaczewski, M. & Frangogiannis, N. G. TGF-\u03b2 signaling in fibrosis. Growth Factors Chur Switz. 29, 196\u2013202 (2011).","journal-title":"Growth Factors Chur Switz."},{"key":"25216_CR60","doi-asserted-by":"publisher","first-page":"55","DOI":"10.2147\/DMSO.S432173","volume":"17","author":"C Guo","year":"2024","unstructured":"Guo, C. et al. Claudin-2 mediates the proximal tubular epithelial cell and ndash;fibroblast crosstalk via paracrine CTGF. Diabetes Metab. Syndr. Obes. 17, 55\u201373 (2024).","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"25216_CR61","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1038\/s41418-018-0175-7","volume":"26","author":"L Yao","year":"2019","unstructured":"Yao, L. et al. Paracrine signalling during ZEB1-mediated epithelial\u2013mesenchymal transition augments local myofibroblast differentiation in lung fibrosis. Cell Death Differ. 26, 943\u2013957 (2019).","journal-title":"Cell Death Differ."},{"key":"25216_CR62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41419-019-1820-x","volume":"10","author":"C Hill","year":"2019","unstructured":"Hill, C. et al. Autophagy inhibition-mediated epithelial\u2013mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis. Cell Death Dis. 10, 1\u201311 (2019).","journal-title":"Cell Death Dis."},{"key":"25216_CR63","doi-asserted-by":"publisher","first-page":"5405","DOI":"10.7150\/ijbs.75876","volume":"18","author":"Y Li","year":"2022","unstructured":"Li, Y. et al. The role of IL-6 in fibrotic diseases: Molecular and cellular mechanisms. Int. J. Biol. Sci. 18, 5405\u20135414 (2022).","journal-title":"Int. J. Biol. Sci."},{"key":"25216_CR64","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.tcb.2020.07.003","volume":"30","author":"B Bakir","year":"2020","unstructured":"Bakir, B., Chiarella, A. M., Pitarresi, J. R. & Rustgi, A. K. EMT, MET, plasticity, and tumor metastasis. Trends Cell Biol. 30, 764\u2013776 (2020).","journal-title":"Trends Cell Biol."},{"key":"25216_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107144","volume":"202","author":"L Luo","year":"2024","unstructured":"Luo, L. et al. The role of epithelial cells in fibrosis: Mechanisms and treatment. Pharmacol. Res. 202, 107144 (2024).","journal-title":"Pharmacol. Res."},{"key":"25216_CR66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002487","volume":"22","author":"T Celi\u00e0-Terrassa","year":"2024","unstructured":"Celi\u00e0-Terrassa, T. & Kang, Y. How important is EMT for cancer metastasis?. PLOS Biol. 22, e3002487 (2024).","journal-title":"PLOS Biol."},{"key":"25216_CR67","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.737570","volume":"12","author":"S Lovisa","year":"2021","unstructured":"Lovisa, S. Epithelial-to-mesenchymal transition in fibrosis: Concepts and targeting strategies. Front. Pharmacol. 12, 737570 (2021).","journal-title":"Front. Pharmacol."},{"key":"25216_CR68","doi-asserted-by":"publisher","first-page":"8104","DOI":"10.1039\/C8RA08659A","volume":"9","author":"Y Qiu","year":"2019","unstructured":"Qiu, Y., Pan, X. & Hu, Y. Polydatin ameliorates pulmonary fibrosis by suppressing inflammation and the epithelial mesenchymal transition via inhibiting the TGF-\u03b2\/Smad signaling pathway. RSC Adv. 9, 8104\u20138112 (2019).","journal-title":"RSC Adv."},{"key":"25216_CR69","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/s10565-024-09858-5","volume":"40","author":"Y-J Lee","year":"2024","unstructured":"Lee, Y.-J., Kim, M., Kim, H.-S. & Kang, J. L. Administration of Gas6 attenuates lung fibrosis via inhibition of the epithelial-mesenchymal transition and fibroblast activation. Cell Biol. Toxicol. 40, 20 (2024).","journal-title":"Cell Biol. Toxicol."},{"key":"25216_CR70","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1038\/s41374-021-00617-2","volume":"101","author":"L Chen","year":"2021","unstructured":"Chen, L. et al. Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial\u2013mesenchymal transition inhibition in vitro and in vivo. Lab. Invest. 101, 1166\u20131175 (2021).","journal-title":"Lab. Invest."},{"key":"25216_CR71","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110241","volume":"128","author":"Y He","year":"2020","unstructured":"He, Y. et al. Salvianolic acid B attenuates epithelial-mesenchymal transition in renal fibrosis rats through activating Sirt1-mediated autophagy. Biomed. Pharmacother. Biomedecine Pharmacother. 128, 110241 (2020).","journal-title":"Biomed. Pharmacother. Biomedecine Pharmacother."},{"key":"25216_CR72","doi-asserted-by":"publisher","first-page":"100531","DOI":"10.1016\/j.jbc.2021.100531","volume":"296","author":"M Yu","year":"2021","unstructured":"Yu, M. et al. Vitamin D receptor inhibits EMT via regulation of the epithelial mitochondrial function in intestinal fibrosis. J. Biol. Chem. 296, 100531 (2021).","journal-title":"J. Biol. Chem."},{"key":"25216_CR73","first-page":"2710509","volume":"2019","author":"L Meng","year":"2019","unstructured":"Meng, L. et al. Yangyin Yiqi Mixture Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats through Inhibiting TGF-\u03b21\/Smad pathway and epithelial to mesenchymal transition. Evid.-Based Compl. Altern. Med. ECAM 2019, 2710509 (2019).","journal-title":"Evid.-Based Compl. Altern. Med. ECAM"},{"key":"25216_CR74","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ejphar.2018.10.008","volume":"842","author":"T-T Gu","year":"2019","unstructured":"Gu, T.-T. et al. Pterostilbene alleviates fructose-induced renal fibrosis by suppressing TGF-\u03b21\/TGF-\u03b2 type I receptor\/Smads signaling in proximal tubular epithelial cells. Eur. J. Pharmacol. 842, 70\u201378 (2019).","journal-title":"Eur. J. Pharmacol."},{"key":"25216_CR75","doi-asserted-by":"publisher","first-page":"121","DOI":"10.31083\/j.fbl2806121","volume":"28","author":"M Wu","year":"2023","unstructured":"Wu, M., Lin, J., Huang, D., Ye, C. & Chen, D. Salvianolic Acid C inhibits the epithelial-mesenchymal transition and ameliorates renal tubulointerstitial fibrosis. Front. Biosci.-Landmark 28, 121 (2023).","journal-title":"Front. Biosci.-Landmark"},{"key":"25216_CR76","doi-asserted-by":"publisher","first-page":"4036","DOI":"10.3390\/jcm9124036","volume":"9","author":"F Aiello","year":"2020","unstructured":"Aiello, F. et al. CannabinEYEds: The endocannabinoid system as a regulator of the ocular surface nociception, inflammatory response, neovascularization and wound healing. J. Clin. Med. 9, 4036 (2020).","journal-title":"J. Clin. Med."},{"key":"25216_CR77","doi-asserted-by":"publisher","first-page":"310","DOI":"10.3390\/biom11020310","volume":"11","author":"M Sisto","year":"2021","unstructured":"Sisto, M., Ribatti, D. & Lisi, S. Organ fibrosis and autoimmunity: The role of inflammation in TGF\u03b2-Dependent EMT. Biomolecules 11, 310 (2021).","journal-title":"Biomolecules"},{"key":"25216_CR78","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.3390\/cells11152336","volume":"11","author":"S Hachana","year":"2022","unstructured":"Hachana, S. & Larriv\u00e9e, B. TGF-\u03b2 superfamily signaling in the eye: Implications for ocular pathologies. Cells 11, 2336 (2022).","journal-title":"Cells"},{"key":"25216_CR79","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1167\/iovs.05-1060","volume":"47","author":"DL Fleenor","year":"2006","unstructured":"Fleenor, D. L. et al. TGF\u03b22-Induced changes in human trabecular meshwork: Implications for intraocular pressure. Investig. Opthalmology Vis. Sci. 47, 226 (2006).","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"25216_CR80","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.exer.2011.06.011","volume":"93","author":"T Tovar-Vidales","year":"2011","unstructured":"Tovar-Vidales, T., Clark, A. F. & Wordinger, R. J. Transforming growth factor-beta2 utilizes the canonical Smad-signaling pathway to regulate tissue transglutaminase expression in human trabecular meshwork cells. Exp. Eye Res. 93, 442\u2013451 (2011).","journal-title":"Exp. Eye Res."},{"key":"25216_CR81","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.1167\/iovs.09-4567","volume":"51","author":"AR Shepard","year":"2010","unstructured":"Shepard, A. R. et al. Adenoviral gene transfer of active human transforming growth factor-\u03b22 elevates intraocular pressure and reduces outflow facility in rodent eyes. Investig. Opthalmology Vis. Sci. 51, 2067 (2010).","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"25216_CR82","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/s12276-022-00778-0","volume":"54","author":"Z Zhao","year":"2022","unstructured":"Zhao, Z. et al. TGF-\u03b2 promotes pericyte-myofibroblast transition in subretinal fibrosis through the Smad2\/3 and Akt\/mTOR pathways. Exp. Mol. Med. 54, 673\u2013684 (2022).","journal-title":"Exp. Mol. Med."},{"key":"25216_CR83","doi-asserted-by":"publisher","first-page":"9672","DOI":"10.1038\/s41598-017-10124-4","volume":"7","author":"X Wang","year":"2017","unstructured":"Wang, X. et al. TGF-\u03b2 participates choroid neovascularization through Smad2\/3-VEGF\/TNF-\u03b1 signaling in mice with Laser-induced wet age-related macular degeneration. Sci. Rep. 7, 9672 (2017).","journal-title":"Sci. Rep."},{"key":"25216_CR84","doi-asserted-by":"publisher","first-page":"5785","DOI":"10.1167\/iovs.18-23789","volume":"59","author":"L Wernecke","year":"2018","unstructured":"Wernecke, L., Keckeis, S., Reichhart, N., Strau\u00df, O. & Salchow, D. J. Epithelial-Mesenchymal transdifferentiation in pediatric lens epithelial cells. Investig. Opthalmology Vis. Sci. 59, 5785 (2018).","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"25216_CR85","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1167\/iovs.64.4.12","volume":"64","author":"F Jiang","year":"2023","unstructured":"Jiang, F. et al. BMP-4 and BMP-7 Inhibit EMT in a model of anterior subcapsular cataract in part by regulating the notch signaling pathway. Invest. Ophthalmol. Vis. Sci. 64, 12 (2023).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"25216_CR86","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029017","volume":"6","author":"CSD Paiva","year":"2011","unstructured":"Paiva, C. S. D. et al. Disruption of TGF-\u03b2 Signaling improves ocular surface epithelial disease in experimental autoimmune keratoconjunctivitis sicca. PLoS ONE 6, e29017 (2011).","journal-title":"PLoS ONE"},{"key":"25216_CR87","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1007\/s004170050144","volume":"236","author":"L Kria","year":"1998","unstructured":"Kria, L., Ohira, A. & Amemiya, T. Growth factors in cultured pterygium fibroblasts: Immunohistochemical and ELISA analysis. Graefes Arch. Clin. Exp. Ophthalmol. 236, 702\u2013708 (1998).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"25216_CR88","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S0065-1281(96)80038-9","volume":"98","author":"L Kria","year":"1996","unstructured":"Kria, L., Ohira, A. & Amemiya, T. Immunohistochemical localization of basic fibroblast growth factor, platelet derived growth factor, transforming growth factor-\u03b2 and tumor necrosis factor-\u03b1 in the pterygium. Acta Histochem. 98, 195\u2013201 (1996).","journal-title":"Acta Histochem."},{"key":"25216_CR89","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.exer.2010.08.025","volume":"91","author":"K Ohtomo","year":"2010","unstructured":"Ohtomo, K. et al. Role of TGF-\u03b2 in tissue eosinophilia associated with vernal keratoconjunctivitis. Exp. Eye Res. 91, 748\u2013754 (2010).","journal-title":"Exp. Eye Res."},{"key":"25216_CR90","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.exer.2004.11.006","volume":"80","author":"N Asano-Kato","year":"2005","unstructured":"Asano-Kato, N. et al. TGF-beta1, IL-1beta, and Th2 cytokines stimulate vascular endothelial growth factor production from conjunctival fibroblasts. Exp. Eye Res. 80, 555\u2013560 (2005).","journal-title":"Exp. Eye Res."},{"key":"25216_CR91","doi-asserted-by":"publisher","first-page":"5465","DOI":"10.1167\/iovs.15-16683","volume":"56","author":"X Zhu","year":"2015","unstructured":"Zhu, X. et al. Evaluation of chitosan\/aptamer targeting TGF-\u03b2 receptor II thermo-sensitive gel for scarring in rat glaucoma filtration surgery. Investig. Opthalmology Vis. Sci. 56, 5465 (2015).","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"25216_CR92","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.exer.2012.11.017","volume":"107","author":"MJ Benito","year":"2013","unstructured":"Benito, M. J. et al. Effect of TGF-\u03b2 on ocular surface epithelial cells. Exp. Eye Res. 107, 88\u2013100 (2013).","journal-title":"Exp. Eye Res."},{"key":"25216_CR93","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.18632\/aging.101050","volume":"8","author":"Z-Y Li","year":"2016","unstructured":"Li, Z.-Y., Chen, Z.-L., Zhang, T., Wei, C. & Shi, W.-Y. TGF-\u03b2 and NF-\u03baB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response. Aging 8, 2337\u20132354 (2016).","journal-title":"Aging"},{"key":"25216_CR94","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109207","volume":"223","author":"F Gao","year":"2022","unstructured":"Gao, F. et al. Elimination of senescent cells inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells. Exp. Eye Res. 223, 109207 (2022).","journal-title":"Exp. Eye Res."},{"key":"25216_CR95","first-page":"189","volume":"11","author":"Y-Y Chen","year":"2018","unstructured":"Chen, Y.-Y. et al. Anti-fibrotic effect of rosmarinic acid on inhibition of pterygium epithelial cells. Int. J. Ophthalmol. 11, 189\u2013195 (2018).","journal-title":"Int. J. Ophthalmol."},{"key":"25216_CR96","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1111\/j.1365-2222.2010.03626.x","volume":"41","author":"A Leonardi","year":"2011","unstructured":"Leonardi, A. et al. Transforming growth factor-\u03b2\/Smad - signalling pathway and conjunctival remodelling in vernal keratoconjunctivitis. Clin. Exp. Allergy 41, 52\u201360 (2011).","journal-title":"Clin. Exp. Allergy"},{"key":"25216_CR97","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/S0002-9440(10)63153-7","volume":"164","author":"S Saika","year":"2004","unstructured":"Saika, S. et al. Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury. Am. J. Pathol. 164, 651\u2013663 (2004).","journal-title":"Am. J. Pathol."},{"key":"25216_CR98","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15569527.2019.1685534","volume":"39","author":"PRA Zantut","year":"2020","unstructured":"Zantut, P. R. A. et al. Effects of cannabis and its components on the retina: A systematic review. Cutan. Ocul. Toxicol. 39, 1\u20139 (2020).","journal-title":"Cutan. Ocul. Toxicol."},{"key":"25216_CR99","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jtos.2021.12.008","volume":"23","author":"BN Tran","year":"2022","unstructured":"Tran, B. N. et al. Topical application of cannabinoid-ligands ameliorates experimental dry-eye disease. Ocul. Surf. 23, 131\u2013139 (2022).","journal-title":"Ocul. Surf."},{"key":"25216_CR100","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1089\/can.2017.0041","volume":"3","author":"D Thapa","year":"2018","unstructured":"Thapa, D. et al. The cannabinoids \u03948THC, CBD, and HU-308 act via distinct receptors to reduce corneal pain and inflammation. Cannabis Cannabinoid Res. 3, 11\u201320 (2018).","journal-title":"Cannabis Cannabinoid Res."},{"key":"25216_CR101","doi-asserted-by":"publisher","first-page":"3338","DOI":"10.3390\/molecules24183338","volume":"24","author":"RF Porter","year":"2019","unstructured":"Porter, R. F. et al. Selective cannabinoid 2 receptor agonists as potential therapeutic drugs for the treatment of endotoxin-induced uveitis. Molecules 24, 3338 (2019).","journal-title":"Molecules"},{"key":"25216_CR102","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.prostaglandins.2018.09.004","volume":"139","author":"JT Toguri","year":"2018","unstructured":"Toguri, J. T. et al. Inflammation and CB2 signaling drive novel changes in the ocular lipidome and regulate immune cell activity in the eye. Prostaglandins Other Lipid Mediat. 139, 54\u201362 (2018).","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"25216_CR103","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1111\/bph.12545","volume":"171","author":"JT Toguri","year":"2014","unstructured":"Toguri, J. T. et al. Anti-inflammatory effects of cannabinoid CB2 receptor activation in endotoxin-induced uveitis. Br. J. Pharmacol. 171, 1448\u20131461 (2014).","journal-title":"Br. J. Pharmacol."},{"key":"25216_CR104","doi-asserted-by":"publisher","first-page":"238","DOI":"10.2492\/inflammregen.33.238","volume":"33","author":"Y Ogawa","year":"2013","unstructured":"Ogawa, Y. & Tsubota, K. Dry eye disease and inflammation. Inflamm. Regen. 33, 238\u2013248 (2013).","journal-title":"Inflamm. Regen."},{"key":"25216_CR105","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1097\/00003226-199004000-00014","volume":"9","author":"R Hemady","year":"1990","unstructured":"Hemady, R., Chu, W. & Foster, C. S. Keratoconjunctivitis sicca and corneal ulcers. Cornea 9, 170\u2013173 (1990).","journal-title":"Cornea"},{"key":"25216_CR106","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.2147\/OPTH.S465143","volume":"18","author":"PK Gupta","year":"2024","unstructured":"Gupta, P. K. et al. Tolerability of current treatments for dry eye disease: A review of approved and investigational therapies. Clin. Ophthalmol. Auckl. NZ 18, 2283\u20132302 (2024).","journal-title":"Clin. Ophthalmol. Auckl. NZ"},{"key":"25216_CR107","doi-asserted-by":"publisher","first-page":"S34","DOI":"10.1016\/j.ophtha.2017.08.004","volume":"124","author":"G Dieckmann","year":"2017","unstructured":"Dieckmann, G., Goyal, S. & Hamrah, P. Neuropathic corneal pain approaches for management. Ophthalmology 124, S34\u2013S47 (2017).","journal-title":"Ophthalmology"},{"key":"25216_CR108","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1097\/j.jcrs.0000000000001225","volume":"49","author":"JD Lafreniere","year":"2023","unstructured":"Lafreniere, J. D., Szczesniak, A.-M., Courtney, E., Kelly, M. E. M. & Faktorovich, E. G. Topical analgesics for acute corneal pain: Current options and emerging therapeutics. J. Cataract Refract. Surg. 49, 1160\u20131167 (2023).","journal-title":"J. Cataract Refract. Surg."},{"key":"25216_CR109","first-page":"429","volume":"20","author":"VB Pereira","year":"2017","unstructured":"Pereira, V. B., Garcia, R., Torricelli, A. A. & Bechara, S. J. Opioids for ocular pain - a narrative review. Pain Physician 20, 429\u2013436 (2017).","journal-title":"Pain Physician"},{"key":"25216_CR110","first-page":"89","volume":"10","author":"M Inomata","year":"2015","unstructured":"Inomata, M., Nishioka, Y. & Azuma, A. Nintedanib: Evidence for its therapeutic potential in idiopathic pulmonary fibrosis. Core Evid. 10, 89\u201398 (2015).","journal-title":"Core Evid."},{"key":"25216_CR111","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121048","volume":"309","author":"SA Antar","year":"2022","unstructured":"Antar, S. A., Saleh, M. A. & Al-Karmalawy, A. A. Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and\/or anti-SARS-CoV-2. Life Sci. 309, 121048 (2022).","journal-title":"Life Sci."},{"key":"25216_CR112","doi-asserted-by":"publisher","first-page":"22098","DOI":"10.18632\/oncotarget.4300","volume":"6","author":"RY-J Huang","year":"2015","unstructured":"Huang, R.Y.-J. et al. Functional relevance of a six mesenchymal gene signature in epithelial-mesenchymal transition (EMT) reversal by the triple angiokinase inhibitor, nintedanib (BIBF1120). Oncotarget 6, 22098\u201322113 (2015).","journal-title":"Oncotarget"},{"key":"25216_CR113","doi-asserted-by":"publisher","first-page":"944","DOI":"10.3892\/ol.2017.6188","volume":"14","author":"R Kurimoto","year":"2017","unstructured":"Kurimoto, R. et al. Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma. Oncol. Lett. 14, 944\u2013950 (2017).","journal-title":"Oncol. Lett."},{"key":"25216_CR114","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.resinv.2020.01.003","volume":"58","author":"H Ihara","year":"2020","unstructured":"Ihara, H. et al. Nintedanib inhibits epithelial-mesenchymal transition in A549 alveolar epithelial cells through regulation of the TGF-\u03b2\/Smad pathway. Respir. Investig. 58, 275\u2013284 (2020).","journal-title":"Respir. Investig."},{"key":"25216_CR115","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.hrtlng.2025.05.008","volume":"73","author":"S Cheema","year":"2025","unstructured":"Cheema, S. et al. Efficacy and safety of Nintedanib in idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Heart Lung 73, 114\u2013122 (2025).","journal-title":"Heart Lung"},{"key":"25216_CR116","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-050004","volume":"11","author":"W Wu","year":"2021","unstructured":"Wu, W., Qiu, L., Wu, J., Liu, X. & Zhang, G. Efficacy and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis patients: A systematic review and meta-analysis of randomised controlled trials. BMJ Open 11, e050004 (2021).","journal-title":"BMJ Open"},{"key":"25216_CR117","first-page":"2305","volume":"107","author":"K Singh","year":"2000","unstructured":"Singh, K. et al. Trabeculectomy with intraoperative mitomycin C versus 5-fluorouracil. Pros. Rand. Clin. Trial. Ophthalmology 107, 2305\u20132309 (2000).","journal-title":"Pros. Rand. Clin. Trial. Ophthalmology"},{"key":"25216_CR118","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e15368","volume":"9","author":"AG Shukla","year":"2023","unstructured":"Shukla, A. G., Milman, T., Fertala, J., Steplewski, A. & Fertala, A. Scar formation in the presence of mitomycin C and the anti-fibrotic antibody in a rabbit model of glaucoma microsurgery: A pilot study. Heliyon 9, e15368 (2023).","journal-title":"Heliyon"},{"key":"25216_CR119","first-page":"580","volume":"26","author":"MS Shapiro","year":"1985","unstructured":"Shapiro, M. S., Thoft, R. A., Friend, J., Parrish, R. K. & Gressel, M. G. 5-Fluorouracil toxicity to the ocular surface epithelium. Invest. Ophthalmol. Vis. Sci. 26, 580\u2013583 (1985).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"25216_CR120","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1097\/IJG.0000000000000741","volume":"26","author":"Z Vahedian","year":"2017","unstructured":"Vahedian, Z. et al. Short-term results of trabeculectomy using adjunctive intracameral bevacizumab versus mitomycin C: A randomized controlled trial. J. Glaucoma 26, 829 (2017).","journal-title":"J. Glaucoma"},{"key":"25216_CR121","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1016\/j.ophtha.2007.03.050","volume":"114","author":"CAT-152 0102 Trabeculectomy Study Group","year":"2007","unstructured":"CAT-152 0102 Trabeculectomy Study Group et al. A phase III study of subconjunctival human anti-transforming growth factor beta (2) monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy. Ophthalmology 114, 1822\u20131830 (2007).","journal-title":"Ophthalmology"},{"key":"25216_CR122","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112423","volume":"137","author":"G Massoud","year":"2024","unstructured":"Massoud, G. et al. Unlocking the potential of tranilast: Targeting fibrotic signaling pathways for therapeutic benefit. Int. Immunopharmacol. 137, 112423 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"25216_CR123","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3109\/02713683.2012.658593","volume":"37","author":"MS Spitzer","year":"2012","unstructured":"Spitzer, M. S. et al. Biocompatibility and antifibrotic effect of UV-cross-linked hyaluronate as a release-system for tranilast after trabeculectomy in a rabbit model\u2014a pilot study. Curr. Eye Res. 37, 463\u2013470 (2012).","journal-title":"Curr. Eye Res."},{"key":"25216_CR124","first-page":"51","volume":"27","author":"S Li","year":"2014","unstructured":"Li, S., Liu, Q., He, A. & Wu, F. Tranilast attenuates TGF-\u03b21-induced epithelial-mesenchymal transition in the NRK-52E cells. Pak. J. Pharm. Sci. 27, 51\u201355 (2014).","journal-title":"Pak. J. Pharm. Sci."},{"key":"25216_CR125","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2021.1925293","author":"A Saeedi-Boroujeni","year":"2021","unstructured":"Saeedi-Boroujeni, A. et al. Tranilast: A potential anti-Inflammatory and NLRP3 inflammasome inhibitor drug for COVID-19. Immunopharmacol. Immunotoxicol. https:\/\/doi.org\/10.1080\/08923973.2021.1925293 (2021).","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"25216_CR126","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12964-023-01372-1","volume":"22","author":"J Cao","year":"2024","unstructured":"Cao, J., Jiao, M., Kou, Z., Han, F. & Dong, L. SB431542 partially inhibits high glucose-induced EMT by restoring mitochondrial homeostasis in RPE cells. Cell Commun. Signal. CCS 22, 17 (2024).","journal-title":"Cell Commun. Signal. CCS"},{"key":"25216_CR127","doi-asserted-by":"publisher","first-page":"4152","DOI":"10.1021\/acs.molpharmaceut.0c00633","volume":"17","author":"J Zhang","year":"2020","unstructured":"Zhang, J. et al. SB431542-Loaded liposomes alleviate liver fibrosis by suppressing TGF-\u03b2 signaling. Mol. Pharm. 17, 4152\u20134162 (2020).","journal-title":"Mol. Pharm."},{"key":"25216_CR128","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1093\/carcin\/bgq191","volume":"31","author":"L Mordasky Markell","year":"2010","unstructured":"Mordasky Markell, L., P\u00e9rez-Lorenzo, R., Masiuk, K. E., Kennett, M. J. & Glick, A. B. Use of a TGF\u03b2 type I receptor inhibitor in mouse skin carcinogenesis reveals a dual role for TGF\u03b2 signaling in tumor promotion and progression. Carcinogenesis 31, 2127\u20132135 (2010).","journal-title":"Carcinogenesis"},{"key":"25216_CR129","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1089\/can.2016.0034","volume":"2","author":"K Iffland","year":"2017","unstructured":"Iffland, K. & Grotenhermen, F. An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2, 139\u2013154 (2017).","journal-title":"Cannabis Cannabinoid Res."},{"key":"25216_CR130","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1089\/jop.2018.0141","volume":"35","author":"P Taskar","year":"2019","unstructured":"Taskar, P. et al. Analog derivatization of cannabidiol for improved ocular permeation. J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther. 35, 301\u2013310 (2019).","journal-title":"J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther."},{"key":"25216_CR131","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.121627","volume":"617","author":"L Rebibo","year":"2022","unstructured":"Rebibo, L., Fru\u0161i\u0107-Zlotkin, M., Ofri, R., Nassar, T. & Benita, S. The dose-dependent effect of a stabilized cannabidiol nanoemulsion on ocular surface inflammation and intraocular pressure. Int. J. Pharm. 617, 121627 (2022).","journal-title":"Int. J. Pharm."},{"key":"25216_CR132","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.3390\/pharmaceutics14122585","volume":"14","author":"S Senapati","year":"2022","unstructured":"Senapati, S. et al. Cannabidiol loaded topical ophthalmic nanoemulsion lowers intraocular pressure in normotensive dutch-belted rabbits. Pharmaceutics 14, 2585 (2022).","journal-title":"Pharmaceutics"},{"key":"25216_CR133","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3390\/pharmaceutics10010028","volume":"10","author":"RD Bachu","year":"2018","unstructured":"Bachu, R. D., Chowdhury, P., Al-Saedi, Z. H. F., Karla, P. K. & Boddu, S. H. S. Ocular drug delivery barriers\u2014role of nanocarriers in the treatment of anterior segment ocular diseases. Pharmaceutics 10, 28 (2018).","journal-title":"Pharmaceutics"},{"key":"25216_CR134","first-page":"3587","volume":"8","author":"Y Wu","year":"2013","unstructured":"Wu, Y., Yao, J., Zhou, J. & Dahmani, F. Z. Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels. Int. J. Nanomed. 8, 3587\u20133601 (2013).","journal-title":"Int. J. Nanomed."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25216-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25216-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25216-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T13:04:32Z","timestamp":1763730272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25216-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":134,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["25216"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-25216-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]},"assertion":[{"value":"8 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"41229"}}