TGF-β stimulates biglycan synthesis via p38 and ERK phosphorylation of the linker region of Smad2

被引：83
作者：
Burch, Micah L. [2 ,3 ,4 ]
Yang, Sundy N. Y. [2 ]
Ballinger, Mandy L. [2 ]
Getachew, Robel [2 ]
Osman, Narin [2 ,3 ,4 ]
Little, Peter J. [1 ,2 ,3 ,4 ]
机构：
[1] Baker IDI Heart & Diabet Inst, Diabet & Cell Biol Lab, Melbourne, Vic 8008, Australia
[2] Baker IDI Heart & Diabet Inst, Diabet & Cell Biol Lab, Melbourne, Vic 3004, Australia
[3] Monash Univ, Alfred Hosp, Sch Med, Dept Med, Prahran, Vic 3004, Australia
[4] Monash Univ, Alfred Hosp, Sch Med, Dept Immunol, Prahran, Vic 3004, Australia
来源：
CELLULAR AND MOLECULAR LIFE SCIENCES | 2010年 / 67卷 / 12期
基金：
英国医学研究理事会;
关键词：
MAP kinases; Transforming growth factor-beta; Glycosaminoglycan; Atherosclerosis; Biglycan; GROWTH-FACTOR-BETA; ARTERIAL SMOOTH-MUSCLE; PROTEOGLYCAN SYNTHESIS; INCREASED BINDING; EXPRESSION; CELLS; ATHEROSCLEROSIS; LIPOPROTEINS; DOWNSTREAM; ACTIVATION;
D O I：
10.1007/s00018-010-0315-9
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：
Transforming growth factor (TGF)-beta treatment of human vascular smooth-muscle cells increases the expression of biglycan and causes marked elongation of its glycosaminoglycan (GAG) chains. We investigated the role of MAP kinases and Smad transcription factors in this response. TGF-beta-stimulated phosphorylation of p38, ERK, and JNK as well as Smad2 at both its carboxy terminal (phospho-Smad2C) and in the linker region (phospho-Smad2L). Pharmacological inhibition of ERK and p38 blocked TGF-beta-mediated GAG elongation and expression of biglycan whereas inhibition of JNK had no effect. Inhibition of ERK and p38 but not JNK attenuated the effect of TGF-beta to increase phospho-Smad2L. High levels of phospho-Smad2L were detected in a nuclear fraction of TGF-beta treated cells. Thus, MAP kinase signaling through ERK and p38 and via phosphorylation of the linker region of Smad2 mediates the effects of TGF-beta on biglycan synthesis in vascular smooth-muscle cells.
引用
收藏
页码：2077 / 2090
页数：14
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