TGF-β2 induces transdifferentiation and fibrosis in human lens epithelial cells via regulating gremlin and CTGF

被引：83

作者：

Ma, Bo ^{[1
]}

Kang, Qianyan ^{[2
]}

Qin, Li ^{[2
]}

Cui, Lijun ^{[2
]}

Pei, Cheng ^{[2
]}

机构：

[1] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Xian 710061, Peoples R China

[2] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Dept Ophthalmol, Xian 710061, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2014年 / 447卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Transforming growth factor beta 2; Human lens epithelial cells; Connective tissue growth factor; Gremlin; Extracellular matrix; Smad signaling pathway; TISSUE GROWTH-FACTOR; BONE MORPHOGENETIC PROTEINS; TRABECULAR MESHWORK CELLS; MESENCHYMAL TRANSITION; FACTOR-BETA; EXPRESSION; TRANSFORMING-GROWTH-FACTOR-BETA-2; HOMEOSTASIS; DISEASES; SMAD3;

D O I：

10.1016/j.bbrc.2014.04.068

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Transforming growth factor (TGF)-beta 2, 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-beta 2 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-beta 2, CTGF and gremlin can individually induce the expression of a-smooth muscle actin (alpha-SMA), fibronectin (Fn), collagen type I (COL-I), Smad2 and Smad3 in HLECs. Blockade of CTGF and gremlin effectively inhibited TGF-beta 2-induced expression of alpha-SMA, Fn, COL-I, Smad2, and Smad3 in HLECs. Furthermore blockade of Smad2 and Smad3 effectively inhibited CTGF and gremlin induced expression of alpha-SMA, Fn, COL-I in HLECs. In conclusion, TGF-beta 2, 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-beta 2-induced EMT, ECM synthesis due to failure in activation of Smad signaling pathway in HLECs. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：689 / 695

页数：7

共 30 条

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