Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor-|[bgr]| in mesangial cells

摘要

Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor- in mesangial cells. Transforming growth factor- (TGF-) 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- has been also known as an important player in the pathogenesis of various fibrotic diseases including glomerulosclerosis, signal-transduction cascades of TGF- have remained to be clarified. However, emerging evidence indicates that TGF- 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--induced gene expression of extracellular matrix proteins in mesangial cells. TGF- 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--induced fibronectin expression. These data suggest that MAPKs play an important role in TGF--mediated extracellular matrix production in mesangial cells.