title: TGF-β2 induces transdifferentiation and fibrosis in human lens epithelial cells via regulating gremlin and CTGF.
abstract: Transforming growth factor (TGF)-β2, gremlin and connective tissue growth factor (CTGF) are known to play important roles in the induction of epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) synthesis. However, the complex functional relationship among gremlin, CTGF and TGF-β2 in the induction of EMT and ECM synthesis in human lens epithelial cells (HLECs) has not been reported. In this study, we found that TGF-β2, CTGF and gremlin can individually induce the expression of α-smooth muscle actin (α-SMA), fibronectin (Fn), collagen type I (COL-I), Smad2 and Smad3 in HLECs. Blockade of CTGF and gremlin effectively inhibited TGF-β2-induced expression of α-SMA, Fn, COL-I, Smad2, and Smad3 in HLECs. Furthermore blockade of Smad2 and Smad3 effectively inhibited CTGF and gremlin induced expression of α-SMA, Fn, COL-I in HLECs. In conclusion, TGF-β2, CTGF and gremlin are all involved in EMT and ECM synthesis via activation of Smad signaling pathway in HLECs. Specifically silencing CTGF and gremlin can effectively block the TGF-β2-induced EMT, ECM synthesis due to failure in activation of Smad signaling pathway in HLECs.
authors.affiliation: Medical School of Xi'an Jiaotong University, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Ophthalmology, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Qianyan
authors.initials: Q
authors.lastname: Kang
authors.affiliation: Department of Ophthalmology, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Ophthalmology, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Ophthalmology, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: peich71@163.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Pei
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D058442:Capsule Opacification / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D054338:Cell Transdifferentiation / Q000502:physiology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D057852:Posterior Capsule of the Lens / Q000378:metabolism* / Q000473:pathology*; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C526317:CCN2 protein, human; D015820:Cadherins; D024042:Collagen Type I; D005353:Fibronectins; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053781:Transforming Growth Factor beta2; D055513:Connective Tissue Growth Factor
keywords: Connective tissue growth factor; Extracellular matrix; Gremlin; Human lens epithelial cells; Smad signaling pathway; Transforming growth factor β2