Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor-β in mesangial cells

被引：42

作者：

Inoki, K ^{[1
]}

Haneda, M ^{[1
]}

Ishida, T ^{[1
]}

Mori, H ^{[1
]}

Maeda, S ^{[1
]}

Koya, D ^{[1
]}

Sugimoto, T ^{[1
]}

Kikkawa, R ^{[1
]}

机构：

[1] Shiga Univ Med Sci, Dept Med 3, Otsu, Shiga 5202192, Japan

来源：

KIDNEY INTERNATIONAL | 2000年 / 58卷

关键词：

Smad; fibronectin; extracellular matrix;

D O I：

10.1046/j.1523-1755.2000.07712.x

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell proliferation, differentiation, and production of extracellular matrix proteins in various types of cells including mesangial cells. Although TGF-beta has been also known as an important player in the pathogenesis of various fibrotic diseases including glomerulosclerosis, signal-transduction cascades of TGF-beta have remained to be clarified. However, emerging evidence indicates that TGF-beta can activate various signal transduction cascades such as Smad proteins and mitogen-activated protein kinases (MAPKs) in many types of cells. Here, we examine the role of MAPKs in TGF-beta-induced gene expression of extracellular matrix proteins in mesangial cells. TGF-beta increases extracellular signal-regulated kinase (ERK) activity, one of the MAPKs, and the expression of fibronectin mRNA and protein in rat mesangial cells. Furthermore, PD98059, a specific inhibitor of MAPK/ERK kinase (MEK), can inhibit this TGF-beta-induced fibronectin expression. These data suggest that MAPKs play an important role in TGF-beta-mediated extracellular matrix production in mesangial cells.

引用

页码：S76 / S80

页数：5

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