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

Bo Ma; Qianyan Kang; Li Qin; Lijun Cui; Cheng Pei

doi:10.1016/j.bbrc.2014.04.068

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

Biochem Biophys Res Commun. 2014 May 16;447(4):689-95. doi: 10.1016/j.bbrc.2014.04.068. Epub 2014 Apr 19.

Authors

Bo Ma¹, Qianyan Kang², Li Qin², Lijun Cui², Cheng Pei³

Affiliations

¹ Medical School of Xi'an Jiaotong University, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710061, China.
² Department of Ophthalmology, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710061, China.
³ Department of Ophthalmology, First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: peich71@163.com.

PMID: 24755068
DOI: 10.1016/j.bbrc.2014.04.068

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.

Keywords: Connective tissue growth factor; Extracellular matrix; Gremlin; Human lens epithelial cells; Smad signaling pathway; Transforming growth factor β2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Actins / metabolism
Cadherins / genetics
Cadherins / metabolism
Capsule Opacification / etiology
Capsule Opacification / metabolism
Capsule Opacification / pathology
Cell Transdifferentiation / physiology
Collagen Type I / genetics
Collagen Type I / metabolism
Connective Tissue Growth Factor / antagonists & inhibitors
Connective Tissue Growth Factor / genetics
Connective Tissue Growth Factor / metabolism*
Epithelial Cells / metabolism
Epithelial Cells / pathology
Epithelial-Mesenchymal Transition / physiology
Extracellular Matrix / metabolism
Fibronectins / genetics
Fibronectins / metabolism
Fibrosis
Humans
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism*
Posterior Capsule of the Lens / metabolism*
Posterior Capsule of the Lens / pathology*
Postoperative Complications / etiology
Postoperative Complications / metabolism
Postoperative Complications / pathology
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / genetics
Signal Transduction
Smad2 Protein / antagonists & inhibitors
Smad2 Protein / genetics
Smad2 Protein / metabolism
Smad3 Protein / antagonists & inhibitors
Smad3 Protein / genetics
Smad3 Protein / metabolism
Transforming Growth Factor beta2 / metabolism*

Substances

ACTA2 protein, human
Actins
CCN2 protein, human
Cadherins
Collagen Type I
Fibronectins
GREM1 protein, human
Intercellular Signaling Peptides and Proteins
RNA, Messenger
RNA, Small Interfering
SMAD2 protein, human
SMAD3 protein, human
Smad2 Protein
Smad3 Protein
Transforming Growth Factor beta2
Connective Tissue Growth Factor