Abstract
Proteases are involved in many biological and physiological processes in the human body. Previously we demonstrated that a serine protease prostasin increased the activity of epithelial sodium channels (ENaC) when the two are co-expressed in Xenopus oocytes. In a mouse cortical collecting duct cell line (M-1 cells), we found that aldosterone increased the secretion of prostasin into culture media, and that prostasin then stimulated 22Na uptake. TGF-β1 has been shown to antagonize the natriferic action of aldosterone in rat collecting ducts. However, the precise mechanisms by which TGF-β1 inhibits the aldosterone-induced sodium entry at the apical membrane are not fully understood. Recently we isolated 2.8kb rat prostasin promoter and studied the transcriptional activity of prostasin promoter in M-1 cells. We found that TGF-β1 substantially decreased the transcriptional activity of prostasin promoter in a dose-dependent manner in M-1 cells. In addition, we found that TGF-β1 inhibited the aldosterone-induced increase in prostasin protein expression in M-1 cells. These results indicate that the possibility that prostasin is an important target molecule for the natriferic and natriuretic hormones to modulate the sodium reabsorption through ENaC in the kidney. [Jpn J Physiol 54 Suppl:S58 (2004)]
