Butyrate and TGF-β Downregulate Na,K-ATPase Expression in Cultured Proximal Tubule Cells

Attempts were made to examine the effect of growth inhibitors on regulation of Na,K-ATPase in primary cultures of renal proximal tubule cells. We observed that both TGF-β and butyrate induced dose dependent decrease of Na,K-ATPase activity. The time course studies showed that the effect of TGF-β preceded the effect of butyrate on inhibition of Na,K-ATPase activity. Both butyrate- and TGF-β-induced inhibition of this enzyme were in general mediated by transcriptional decreases of αand β mRNA and therefore also protein abundance. Like its effect on Na,K-ATPase activity, TGF-β compared to butyrate induced much earlier decline in Na,K-ATPase α and β mRNA and protein abundance. Butyrate did not affect gene expression of TGF-β and anti-TGF-β antibody had no effect on butyrate-induced inhibition of DNA synthesis. Obviously, both butyrate and TGF-β can inhibit the expression of Na,K-ATPase α and β mRNA, but TGF-β does not mediate butyrate′s effect.