{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T14:49:24Z","timestamp":1766587764219,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Purpose: The effects of Rho-associated coiled-coil containing protein kinase (ROCK) 1 and 2 inhibitor, ripasudil hydrochloride hydrate (Rip), ROCK2 inhibitor, KD025 or rosiglitazone (Rosi) on two-dimension (2D) and three-dimension (3D) cultured human conjunctival fibroblasts (HconF) treated by transforming growth factor (TGF\u03b22) were studied. Methods: Two-dimension and three-dimension cultured HconF were examined by transendothelial electrical resistance (TEER, 2D), size and stiffness (3D), and the expression of the extracellular matrix (ECM) including collagen1 (COL1), COL4 and COL6, fibronectin (FN), and \u03b1-smooth muscle actin (\u03b1SMA) by quantitative PCR (2D, 3D) in the presence of Rip, KD025 or Rosi. Results: TGF\u03b22 caused a significant increase in (1) the TEER values (2D) which were greatly reduced by Rosi, (2) the stiffness of the 3D organoids which were substantially reduced by Rip or KD025, and (3) TGF\u03b22 induced a significant up-regulation of all ECMs, except for COL6 (2D) or \u03b1SMA (3D), and down-regulation of COL6 (2D). Rosi caused a significant up-regulation of COL1, 4 and 6 (3D), and down-regulation of COL6 (2D) and \u03b1SMA (3D). Most of these TGF\u03b22-induced expressions in the 2D and \u03b1SMA in the 3D were substantially inhibited by KD025, but COL4 and \u03b1SMA in 2D were further enhanced by Rip. Conclusion: The findings reported herein indicate that TGF\u03b22 induces an increase in fibrogenetic changes on the plane and in the spatial space, and are inhibited by Rosi and ROCK inhibitors, respectively.<\/jats:p>","DOI":"10.3390\/ijms22147335","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T10:42:17Z","timestamp":1625740937000},"page":"7335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Rosiglitasone and ROCK Inhibitors Modulate Fibrogenetic Changes in TGF-\u03b22 Treated Human Conjunctival Fibroblasts (HconF) in Different Manners"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1579-8612","authenticated-orcid":false,"given":"Yuika","family":"Oouchi","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology, School of Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-6532","authenticated-orcid":false,"given":"Megumi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, School of Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5165-6507","authenticated-orcid":false,"given":"Yosuke","family":"Ida","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, School of Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ohguro","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, School of Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0124-5494","authenticated-orcid":false,"given":"Fumihito","family":"Hikage","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, School of Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2174\/1874364101509010049","article-title":"Ocular Surface as Barrier of Innate Immunity","volume":"9","author":"Navas","year":"2015","journal-title":"Open Ophthalmol. J."},{"key":"ref_2","first-page":"386","article-title":"Drug-induced toxic reactions in the eye: An overview","volume":"27","author":"Abdollahi","year":"2004","journal-title":"J. Infus. Nurs. Off. Publ. Infus. Nurses Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/00055735-199604000-00005","article-title":"Current techniques in wound healing modulation in glaucoma surgery","volume":"7","author":"Khaw","year":"1996","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0039-6257(98)00005-8","article-title":"Management of conjunctival cicatrizing diseases and severe ocular surface dysfunction","volume":"43","author":"Chiou","year":"1998","journal-title":"Surv. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S1542-0124(12)70103-9","article-title":"The pathogenesis of pterygium: Current concepts and their therapeutic implications","volume":"6","author":"Chui","year":"2008","journal-title":"Ocul. Surf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1097\/ACI.0000000000000197","article-title":"Linking immune responses with fibrosis in allergic eye disease","volume":"15","author":"Dale","year":"2015","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1097\/OPX.0000000000001071","article-title":"A Review of Ocular Graft-Versus-Host Disease","volume":"94","author":"Munir","year":"2017","journal-title":"Optom. Vis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1097\/00061198-200106000-00017","article-title":"Trabeculectomy, risk factors for failure and the preoperative state of the conjunctiva","volume":"10","author":"Broadway","year":"2001","journal-title":"J. Glaucoma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.exer.2015.03.021","article-title":"Conjunctival fibrosis following filtering glaucoma surgery","volume":"142","author":"Schlunck","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/path.1446","article-title":"Pathogenetic mechanisms in usual interstitial pneumonia\/idiopathic pulmonary fibrosis","volume":"201","author":"White","year":"2003","journal-title":"J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1089\/wound.2013.0429","article-title":"Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring","volume":"2","author":"Finnson","year":"2013","journal-title":"Adv. Wound Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"286s","DOI":"10.1378\/chest.122.6_suppl.286S","article-title":"The myofibroblast in pulmonary fibrosis","volume":"122","author":"Phan","year":"2002","journal-title":"Chest"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1006\/excr.2000.4869","article-title":"Transforming growth factor-beta1 promotes the morphological and functional differentiation of the myofibroblast","volume":"257","author":"Vaughan","year":"2000","journal-title":"Exp. Cell Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1165\/ajrcmb.21.6.3720","article-title":"Inhibition of myofibroblast apoptosis by transforming growth factor beta(1)","volume":"21","author":"Zhang","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.exer.2015.07.009","article-title":"Myofibroblasts","volume":"142","author":"Hinz","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrm809","article-title":"Myofibroblasts and mechano-regulation of connective tissue remodelling","volume":"3","author":"Tomasek","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fphar.2015.00248","article-title":"Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: A computational approach","volume":"6","author":"Platania","year":"2015","journal-title":"Front. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0090-6980(03)00003-0","article-title":"Peroxisome proliferator-activated receptors: A critical review on endogenous pathways for ligand generation","volume":"71","author":"Wray","year":"2003","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s000110050622","article-title":"Peroxisome proliferator-activated receptors (PPARs): Nuclear receptors at the crossroads between lipid metabolism and inflammation","volume":"49","author":"Chinetti","year":"2000","journal-title":"Inflamm. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1021\/jm990554g","article-title":"The PPARs: From orphan receptors to drug discovery","volume":"43","author":"Willson","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/0092-8674(95)90193-0","article-title":"15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma","volume":"83","author":"Forman","year":"1995","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/0092-8674(95)90194-9","article-title":"A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation","volume":"83","author":"Kliewer","year":"1995","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1046\/j.1464-5491.1999.00023.x","article-title":"Thiazolidinediones: A new class of antidiabetic drugs","volume":"16","author":"Day","year":"1999","journal-title":"Diabet. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12953","DOI":"10.1074\/jbc.270.22.12953","article-title":"An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma)","volume":"270","author":"Lehmann","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1046\/j.1432-1033.2003.03937.x","article-title":"Binding analyses between Human PPARgamma-LBD and ligands","volume":"271","author":"Yu","year":"2004","journal-title":"Eur. J. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Luo, Y.H., Ouyang, P.B., Tian, J., Guo, X.J., and Duan, X.C. (2014). Rosiglitazone inhibits TGF-\u03b2 1 induced activation of human Tenon fibroblasts via p38 signal pathway. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105796"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29051","DOI":"10.1074\/jbc.270.49.29051","article-title":"A novel serine\/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes","volume":"270","author":"Leung","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1002\/j.1460-2075.1996.tb00539.x","article-title":"The small GTP-binding protein Rho binds to and activates a 160 kDa Ser\/Thr protein kinase homologous to myotonic dystrophy kinase","volume":"15","author":"Ishizaki","year":"1996","journal-title":"Embo J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"C378","DOI":"10.1152\/ajpcell.90624.2007","article-title":"Rho kinases regulate corneal epithelial wound healing","volume":"295","author":"Yin","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1167\/iovs.07-1122","article-title":"Role of small GTPase Rho in regulating corneal epithelial wound healing","volume":"49","author":"Yin","year":"2008","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1111\/j.1582-4934.2012.01538.x","article-title":"Up-regulation of BMP-2 antagonizes TGF-\u03b21\/ROCK-enhanced cardiac fibrotic signalling through activation of Smurf1\/Smad6 complex","volume":"16","author":"Wang","year":"2012","journal-title":"J. Cell Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Inai, K., Burnside, J.L., Hoffman, S., Toole, B.P., and Sugi, Y. (2013). BMP-2 induces versican and hyaluronan that contribute to post-EMT AV cushion cell migration. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077593"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Scimone, C., Bramanti, P., Ruggeri, A., Donato, L., Alafaci, C., Crisafulli, C., Mucciardi, M., Rinaldi, C., Sidoti, A., and D\u2019Angelo, R. (2016). CCM3\/SERPINI1 bidirectional promoter variants in patients with cerebral cavernous malformations: A molecular and functional study. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0332-0"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jns.2017.06.043","article-title":"Relevance of CCM gene polymorphisms for clinical management of sporadic cerebral cavernous malformations","volume":"380","author":"Rinaldi","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s12031-015-0606-6","article-title":"Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations","volume":"57","author":"Scimone","year":"2015","journal-title":"J. Mol. Neurosci. MN"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7958","DOI":"10.1038\/s41598-020-64674-1","article-title":"Prostaglandin F2\u03b1 agonist-induced suppression of 3T3-L1 cell adipogenesis affects spatial formation of extra-cellular matrix","volume":"10","author":"Ida","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1167\/iovs.61.6.13","article-title":"Prostaglandin F2\u03b1 Agonists Negatively Modulate the Size of 3D Organoids from Primary Human Orbital Fibroblasts","volume":"61","author":"Itoh","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20292","DOI":"10.1038\/s41598-020-77302-9","article-title":"ROCK inhibitors beneficially alter the spatial configuration of TGF\u03b22-treated 3D organoids from a human trabecular meshwork (HTM)","volume":"10","author":"Ota","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.tcb.2011.09.005","article-title":"From 3D cell culture to organs-on-chips","volume":"21","author":"Huh","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14821","DOI":"10.1073\/pnas.95.25.14821","article-title":"Reciprocal interactions between beta1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: A different perspective in epithelial biology","volume":"95","author":"Wang","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1039\/C0AN00609B","article-title":"High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array","volume":"136","author":"Tung","year":"2011","journal-title":"The Analyst"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1210\/en.2018-00272","article-title":"HIF2A-LOX Pathway Promotes Fibrotic Tissue Remodeling in Thyroid-Associated Orbitopathy","volume":"160","author":"Hikage","year":"2019","journal-title":"Endocrinology"},{"key":"ref_43","first-page":"652","article-title":"Rho\/ROCK pathway and neural regeneration: A potential therapeutic target for central nervous system and optic nerve damage","volume":"4","author":"Tan","year":"2011","journal-title":"Int. J. Ophthalmol."},{"key":"ref_44","first-page":"251","article-title":"Rho Kinase Proteins Regulate Global miRNA Expression in Endothelial Cells","volume":"10","author":"Stiles","year":"2013","journal-title":"Cancer Genom. Proteom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0014-5793(96)00811-3","article-title":"ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine\/threonine kinase in mice","volume":"392","author":"Nakagawa","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1076\/ceyr.22.6.470.5489","article-title":"Reduction of intraocular pressure by topical administration of an inhibitor of the Rho-associated protein kinase","volume":"22","author":"Waki","year":"2001","journal-title":"Curr. Eye Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1097\/ICO.0b013e3182281ee1","article-title":"The New Therapeutic Concept of Using a Rho Kinase Inhibitor for the Treatment of Corneal Endothelial Dysfunction","volume":"30","author":"Okumura","year":"2011","journal-title":"Cornea"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Scimone, C., Alibrandi, S., Scalinci, S.Z., Trovato Battagliola, E., D\u2019Angelo, R., Sidoti, A., and Donato, L. (2020). Expression of Pro-Angiogenic Markers Is Enhanced by Blue Light in Human RPE Cells. Antioxidants, 9.","DOI":"10.3390\/antiox9111154"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Donato, L., Scimone, C., Alibrandi, S., Pitruzzella, A., Scalia, F., D\u2019Angelo, R., and Sidoti, A. (2020). Possible A2E Mutagenic Effects on RPE Mitochondrial DNA from Innovative RNA-Seq Bioinformatics Pipeline. Antioxidants, 9.","DOI":"10.3390\/antiox9111158"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/jps.20285","article-title":"Contribution of ROCK in Contraction of Trabecular Meshwork: Proposed Mechanism for Regulating Aqueous Outflow in Monkey and Human Eyes","volume":"94","author":"Nakajima","year":"2005","journal-title":"J. Pharm. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.bbapap.2005.06.015","article-title":"Development of specific Rho-kinase inhibitors and their clinical application","volume":"1754","author":"Tamura","year":"2005","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1007\/s40265-014-0333-2","article-title":"Ripasudil: First Global Approval","volume":"74","year":"2014","journal-title":"Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e773","DOI":"10.1111\/aos.14366","article-title":"Ex vivo excimer laser ablation of cornea guttata and ROCK inhibitor-aided endothelial recolonization of ablated central cornea","volume":"98","author":"Kassumeh","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Maruyama, Y., Ikeda, Y., Mori, K., Yoshii, K., Ueno, M., Yoshikawa, H., Sotozono, C., and Kinoshita, S. (2020). Morphological change and recovery of corneal endothelial cells after rho-associated protein kinase inhibitor eye-drop (ripasudil 0.4%) instillation. Brit. J. Ophthalmol., 2.","DOI":"10.1136\/bjophthalmol-2019-315776"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.exer.2016.07.001","article-title":"The effects of ripasudil (K-115), a Rho kinase inhibitor, on activation of human conjunctival fibroblasts","volume":"149","author":"Futakuchi","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/cbf.3382","article-title":"An in vitro study of scarring formation mediated by human Tenon fibroblasts: Effect of Y-27632, a Rho kinase inhibitor","volume":"37","author":"Ibrahim","year":"2019","journal-title":"Cell Biochem. Funct."},{"key":"ref_57","first-page":"1730","article-title":"Inhibition of p38MAP kinase suppresses fibrogenic reaction in conjunctiva in mice","volume":"13","author":"Yamanaka","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1517\/14728222.11.12.1623","article-title":"Molecular mechanisms of cellular senescence and immortalization of human cells","volume":"11","author":"Kiyono","year":"2007","journal-title":"Expert Opin. Ther. targets"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/labinvest.2008.104","article-title":"PPAR-gamma agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-beta","volume":"89","author":"Kawai","year":"2009","journal-title":"Lab Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1042\/CS20100113","article-title":"Rosiglitazone attenuates development of polycystic kidney disease and prolongs survival in Han:SPRD rats","volume":"119","author":"Dai","year":"2010","journal-title":"Clin. Sci. (London England: 1979)"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/s00417-011-1903-6","article-title":"Rosiglitazone attenuates activation of human Tenon\u2019s fibroblasts induced by transforming growth factor-\u03b21","volume":"250","author":"Fan","year":"2012","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1291\/hypres.31.353","article-title":"Pioglitazone, a thiazolidinedione derivative, attenuates left ventricular hypertrophy and fibrosis in salt-sensitive hypertension","volume":"31","author":"Nakamoto","year":"2008","journal-title":"Hypertens Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.biocel.2010.02.006","article-title":"Peroxisome proliferator-activated receptors gamma reverses hepatic nutritional fibrosis in mice and suppresses activation of hepatic stellate cells in vitro","volume":"42","author":"Yu","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1167\/iovs.18-26526","article-title":"Rosiglitazone Treatment Prevents Postoperative Fibrosis in a Rabbit Model of Glaucoma Filtration Surgery","volume":"60","author":"Zhang","year":"2019","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1080\/10717544.2019.1648590","article-title":"Effects of rosiglitazone\/PHBV drug delivery system on postoperative fibrosis in rabbit glaucoma filtration surgery model","volume":"26","author":"Zhang","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cerbone, A., Toaldo, C., Minelli, R., Ciamporcero, E., Pizzimenti, S., Pettazzoni, P., Roma, G., Dianzani, M.U., Ullio, C., and Ferretti, C. (2012). Rosiglitazone and AS601245 decrease cell adhesion and migration through modulation of specific gene expression in human colon cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040149"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7358","DOI":"10.1167\/iovs.12-10292","article-title":"The effects of transforming growth factor-\u03b22 on the expression of follistatin and activin A in normal and glaucomatous human trabecular meshwork cells and tissues","volume":"53","author":"Fitzgerald","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.exer.2006.12.016","article-title":"Regulation of VEGF mRNA expression and protein secretion by TGF-beta2 in human retinal pigment epithelial cells","volume":"84","author":"Bian","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/1523-1747.ep12493517","article-title":"Human keratinocyte locomotion: The effect of selected cytokines","volume":"98","author":"Sarret","year":"1992","journal-title":"J. Investig. Dermatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"19640","DOI":"10.1038\/srep19640","article-title":"Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm\u2019s canal endothelial cells","volume":"6","author":"Kaneko","year":"2016","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/14\/7335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:27:43Z","timestamp":1760164063000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/14\/7335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,8]]},"references-count":70,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22147335"],"URL":"https:\/\/doi.org\/10.3390\/ijms22147335","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,7,8]]}}}