Trannsforming growth factor beta mimicks the effects of butyrate on cell growth and Na,K-ATPase expression in primary culture of rabbit proximal tubular cells

• Main Authors: Wang Young Kao, 王仰高
• Other Authors: Tang Ming Jer
• Format: Others
• Language: zh-TW
• Published: 1994
• Online Access: http://ndltd.ncl.edu.tw/handle/18533159129278831263

碩士 === 國立成功大學 === 生理學研究所 === 82 === Butyrate, a four carbone fatty acid, has been shown to induce differentiation and inhibit proliferation in many cell lines. But the cellular mechanism is still not known. In primary culture of rabbit proximal tubular cells(PT cells), butyrate upregultes the activities of differentiation marker enzymes such as leucine aminopeptidase (LAP), sodium dependent glucose trans- porter, and gluconeogenic enzyme phosphoenoylpyruvate carboxy- kinase (PEPCK). We previously found that butyrate inhibited proliferation of PT cells, but unexpectedly, decreased activity, protein abundance and gene expression of Na, K-ATPase. TGF-beta, a potent growth and differentiation agent for epithelial cells, was then selected to studywhether it has same effects with butyrate in cultured proximal cells. treatment of TGF-beta(0.5- 5 ng/ml) also decreases Na,K-ATPase activity. Na,K-ATPase alpha and beta protein and mRNA abundance was also decreased by TGF- beta incubation, suggesting that TGF- beta induced decrease of Na,K-ATPase may be via a pretranslational mechanism. The time course study of TGF-beta and butyrate to decrease Na,K-ATPase activity and alpha and beta protein and mRNA abundance revealed that the effect of TGF- beta preceded the effect of butyrate. Moreover, treatment of cycloheximide(20 ug/ml) inhibited butyrate -induced inhibition of Na,K-ATPase gene expression. However, treatment with cycloheximide could not block TGF-beta-induced inhibition of Na, K-ATPase gene expression. In addition, butyrate fails to induce TGF-beta gene expression and anti-TGF-beta 1 antibody cannot block the inhibitory effect of butyrate on thymidine incorporation in cultured proximal tubular cells. These data suggest that TGF-beta can mimicks the effect of butyrate on cell proliferation and Na,K-ATPase of proximal tubular cells, but is not the mediator of butyrate.