Caveolin-1 in mesangial cells suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF

Background. Caveolin is a principal component of caveolae and regulates signaling in caveolae. Mesangial cells contain many caveolae, and thus manipulation of caveolin-1 expression level might be useful to control mesangial cell proliferation, which is an important aggravating factor in many renal diseases. Methods. In the present study, we transfected caveolin-1 cDNA to rat primary mesangial cells and MES13 cells, and examined the effects on Raf-extracellular signal-regulated protein kinase (ERK) kinase (MEK)-mitogen-activated protein (MAP) kinase pathway and cell proliferation stimulated by basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF). Activity of the kinases was analyzed by immunofluorescence labeling and Western blot analysis. Results. The overexpression of caveolin-1 inhibited the activation of Raf-1, MEK-1/2, and MAP kinase induced by either bFGF or PDGF. Furthermore, it suppressed the cell proliferation caused by the cytokines. The effect was specific to the Raf-MEK-MAP kinase pathway, because it did not influence activation of Smad2 induced by transforming growth factor-beta (TGF-beta). On the contrary, expression of a dominant-negative caveolin mutant, DGV-caveolin, augmented activation of MAP kinase. Conclusion. The result showed that overexpression of caveolin-1 in mesangial cells suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF. Because bFGF and PDGF are two major cytokines involved in the mesangioproliferative nephritis, the result implies that introduction of caveolin-1 expression vector is a potential therapeutic tool for the disease.