K. Inoki et al., Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor-beta in mesangial cells, KIDNEY INT, 58, 2000, pp. S76-S80
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine th
at regulates cell proliferation, differentiation, and production of extrace
llular matrix proteins in various types of cells including mesangial cells.
Although TGF-beta has been also known as an important player in the pathog
enesis of various fibrotic diseases including glomerulosclerosis, signal-tr
ansduction cascades of TGF-beta have remained to be clarified. However, eme
rging evidence indicates that TGF-beta can activate various signal transduc
tion 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-be
ta-induced gene expression of extracellular matrix proteins in mesangial ce
lls. TGF-beta increases extracellular signal-regulated kinase (ERK) activit
y, 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. Th
ese data suggest that MAPKs play an important role in TGF-beta-mediated ext
racellular matrix production in mesangial cells.