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学科主题: 临床医学
题名:
Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the ERK pathway are required for connective tissue growth factor to potentiate myofibroblast differentiation
作者: Yang, M; Huang, HC; Li, JZ; Li, DX; Wang, HY
关键词: CTGF ; TGF beta 1 ; Smad
刊名: FASEB JOURNAL
发表日期: 2004-10-01
DOI: 10.1096/fj.04-2357fje
卷: 18, 期:13, 页:1920-+
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
关键词[WOS]: HEPATIC STELLATE CELLS ; TGF-BETA ; RENAL FIBROSIS ; TUBULOINTERSTITIAL FIBROSIS ; GRANULATION-TISSUE ; FACTOR CTGF ; EXPRESSION ; FIBROBLASTS ; FIBRONECTIN ; MECHANISM
英文摘要:

Renal myofibroblasts play a crucial role in the accumulation of excess extracellular matrix during renal fibrosis. Both transforming growth factor-beta1 (TGFbeta1) and connective tissue growth factor (CTGF) are important profibrotic growth factors, which interact in the pathogenesis of fibrosis. In this study, we demonstrate that CTGF alone has no influence on myofibroblast transformation and fibronectin secretion in kidney interstitial fibroblasts, whereas incubation of CTGF in combination with TGFbeta1 enhanced TGFbeta1 responses, including myofibroblast activation, de novo expression of alpha-SMA, and extracellular accumulation of fibronectin. CTGF induced tryrosine phosphorylation of the cytoplasmic domain of the low-density lipoprotein receptor-associated protein (LRP) in fibroblasts, and the LRP-antagonist, receptor-associated protein (RAP) inhibited CTGF-induced tryrosine phosphorylation of LRP. Inhibition of LRP signaling reduced CTGF-mediated synergistic induction of alpha-SMA protein. Furthermore, the potentiating action of CTGF was neither dependent on modulation of TGFbeta1-induced Smad2 phosphorylation and its association with Smad4, nor did it result from nuclear accumulation of activated Smad2. When TGFbeta1-pretreated fibroblasts were incubated with CTGF, activation of ERK1/2 MAPK signaling was observed. Inhibition of ERK activation by the MEK1 inhibitor PD98059 was associated with a reduction of CTGF-promoted alpha-SMA protein expression. Our in vitro studies provide evidence that CTGF potentiates TGFbeta1-mediated myofibroblast differentiation and activates differentiated myofibroblasts.

语种: 英语
WOS记录号: WOS:000224849900026
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66276
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: 1.Peking Univ, Inst Nephrol, Beijing 100034, Peoples R China
2.FibroGen Inc, San Francisco, CA USA
3.Peking Univ, Hosp 1, Div Nephrol, Beijing 100034, Peoples R China

Recommended Citation:
Yang, M,Huang, HC,Li, JZ,et al. Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the ERK pathway are required for connective tissue growth factor to potentiate myofibroblast differentiation[J]. FASEB JOURNAL,2004,18(13):1920-+.
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