Functional characterization of TRAP1-like protein involved in modulating fibrotic processes mediated by TGF-β/Smad signaling in hypertrophic scar fibroblasts

被引：47

作者：

Wang, X. ^{[1
,2
]}

Chu, J. ^{[2
]}

Wen, C. J. ^{[1
]}

Fu, S. B. ^{[1
]}

Qian, Y. L. ^{[1
]}

Wo, Y. ^{[3
]}

Wang, C. ^{[1
]}

Wang, D. R. ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai 200011, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Pediat Surg, Shanghai 200127, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Dept Anat, Shanghai 200025, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2015年 / 332卷 / 02期

基金：

中国国家自然科学基金;

关键词：

TRAP1-like protein (TLP); Hypertrophic scar fibroblasts (HSFb); Fibrosis; GROWTH-FACTOR-BETA; CROSS-TALK; MESANGIAL CELLS; DOWN-REGULATION; MAP KINASE; SMAD; FIBRONECTIN; EXPRESSION; PATHWAYS; ERK;

D O I：

10.1016/j.yexcr.2015.01.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The transforming growth factor-beta 1 (TGF-beta)-mediated signaling pathway is believed to be closely associated with wound healing and scar formation, in which TRAP1-like protein (TLP) plays a role in regulating the balance of Smad2 vs. Smad3 signaling. Our previous study revealed the relation between TLP and collagen synthesis in normal human skin fibroblasts. Here, we present a detailed analysis of the effects of TLP on the process of hypertrophic scar formation and contraction. To explore and verify a contribution of TLP to the pathological mechanism of hypertrophic scar fibroblasts (HSFb), we constructed lentiviral vectors that either overexpressed TLP or encoded small hairpin RNAs (shRNAs) targeting TLP, then we transfected them into HSFb. TLP knockdown in HSFb resulted in reduced levels of cell contraction, type I and type III collagen mRNA transcripts and protein expression, and higher levels of fibronectin (FN) compared to control groups. In addition, knockdown of TLP promoted the phosphorylation of Smad3 but repressed Smad2 and Erk-1/2 phosphorylation in human hypertrophic scar fibroblasts compared to control groups. The reduction of TLP did not interfere with HSF proliferative ability, but exogenous TLP cooperated with TGF-beta 1 to increase cell viability. Together, our findings demonstrate evidence for a contribution of TLP expression in hypertrophic scar formation and contraction. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：202 / 211

页数：10

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