Butyrate and TGF-beta 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-beta and butyrate induced dose dependent decrease of Na,K-ATPase activity. The time course studies showed that the effect of TGF-beta preceded the effect of butyrate on inhibition of Na,K-ATPase activity. Both butyrate- and TGF-beta-induced inhibition of this enzyme were in general mediated by transcriptional decreases of alpha and beta mRNA and therefore also protein abundance. Like its effect on Na,K-ATPase activity, TGF-beta compared to butyrate induced much earlier decline in Na,K-ATPase alpha and beta mRNA and protein abundance. Butyrate did not affect gene expression of TGF-beta and anti-TGF-beta antibody had no effect on butyrate-induced inhibition of DNA synthesis. Obviously, both butyrate and TGF-beta can inhibit the expression of Na,K-ATPase alpha and beta mRNA, but TGF-beta does not mediate butyrate's effect.