Interaction of ERK1/2 and Smad2/3 signaling pathways in TGF-β1-induced TIMP-3 expression in rat chondrocytes

被引：13

作者：

Wang, Xiang ^{[1
,2
]}

Zhu, Yanhui ^{[1
]}

Tao, Hairong ^{[1
]}

Jin, Chen ^{[1
]}

Liu, Yonzhang ^{[1
]}

Lu, Xiongwei ^{[1
]}

Hu, Xiaopeng ^{[1
]}

Fan, Cunyi ^{[2
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 3, Dept Orthopaed, Shanghai 200030, Peoples R China

[2] Shanghai Jiao Tong Univ, Affiliated Hosp 6, Dept Orthopaed, Shanghai 200030, Peoples R China

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2014年 / 564卷

基金：

中国国家自然科学基金;

关键词：

Transforming growth factor beta1; TIMP-3; ERK1/2; Smad2/3; Chondrocytes; GROWTH-FACTOR-BETA; TGF-BETA; ARTICULAR CHONDROCYTES; TISSUE INHIBITOR; CROSS-TALK; TNF-ALPHA; METALLOPROTEINASES-3; GENE; MAP KINASE; CELLS; CARTILAGE;

D O I：

10.1016/j.abb.2014.09.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is an important natural inhibitor of matrix metalloproteinases (MMPs) and of a disintegrin and metalloproteinase with thrombospondin motif (ADAMTs), which can cleave cartilage extracellular matrix components to cause cartilage degradation. In this study, our data suggest TGF-beta 1 induces TIMP-3 expression through activations of both the ERKI/2 and Smad2/3 signaling pathways. TGF-beta 1-stimulated TIMP-3 expression was significantly inhibited by SB525334 (TGF11 beta receptor I kinase inhibitor), accompanied by a reduction in ERKI/2 and Smad3 phosphorylation. We used P098059 (MEK inhibitor) and SIS3 (inhibitor of Smad3 phosphorylation) to investigate the respective roles of ERKI/2 and Smad2/3 signaling pathways in TGF-beta 1-induced TIMP-3 expression. The results show PD98059 treatment significantly suppressed TGF-beta 1-induced ERKI/2 phosphorylation and TIMP-3 expression. Under these conditions, the degree of Smad3 phosphorylation correlated with ERK1/2 activation, which suggests that ERK1/2 may activate Smad3 phosphorylation. SIS3 significantly inhibited TGF-beta 1-induced Smad3 phosphorylation and TIMP-3 expression. ERKI/2 phosphorylation alone had no effect on TGF-beta 1-induced TIMP-3 expression, which suggests ERKI/2 via Smad3 phosphorylation regulates TGF-beta 1 -induced TIMP-3 expression. Here, we demonstrate that ERKI/2 may be capable of activating the Smad2/3 signaling pathway to result in TGF-beta 1-induced TIMP-3 up-regulation. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：229 / 236

页数：8