Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor-beta in mesangial cells.
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.
Inoki
K
K
The Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Japan.
Haneda
M
M
Ishida
T
T
Mori
H
H
Maeda
S
S
Koya
D
D
Sugimoto
T
T
Kikkawa
R
R
D000818:Animals; D005353:Fibronectins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000502:physiology*
D005353:Fibronectins; D016212:Transforming Growth Factor beta; D020928:Mitogen-Activated Protein Kinases