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1: Kidney Int Suppl. 2000 Sep;77:S76-80.Links

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

Inoki K, Haneda M, Ishida T, Mori H, Maeda S, Koya D, Sugimoto T, Kikkawa R.

The Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Japan.

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.

PMID: 10997694 [PubMed - indexed for MEDLINE]