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- Title
Transforming growth factor-{beta}1 decreases epithelial sodium channel functionality in renal collecting duct cells via a Smad4-dependent pathway.
- Authors
Chiz-Tzung Chang; Cheng-Chieh Hung; Yung-Chang Chen; Tzung-Hai Yen; Mai-Szu Wu; Chih-Wei Yang; Aled Phillips; Ya-Chung Tian
- Abstract
Background. Transformation growth factor-β1 (TGF-β1) inhibits transepithelial sodium transport and suppresses the epithelial sodium channel (ENaC) in many different types of epithelial cells; however, the molecular mechanism of this effect in the kidney is still not clear. The aim of this study was to examine the regulation of transepithelial sodium transport by TGF-β1 in renal cells. Methods. We derived stable mouse cortical collecting duct cell lines that overexpressed Smad4 or N-termianl truncated Smad4, and studied the effects of TGF-β1 on them. The equivalent electrical current (Ieq) was taken as representing transepithelial current and the amiloride sensitive short circuit current (AmsIsc) as representing the ENaC activity. We used real-time PCR to quantify the expression of ENaC and measurement of the luciferase activity of cells transiently transfected with a mouse α-ENaC promoter to assess the α-ENaC promoter activity. Result. The administration of TGF-β1 decreased Ieq, mainly as a result of the decrease of AmsIsc, and it correlated with inhibition of the α-ENaC mRNA expression. The overexpression of Smad4 led to a decrease in AmsIsc, α-ENaC mRNA and α-ENaC promoter activity, but the overexpression of the N-terminal truncated Smad4 did not induce these changes. The TGF-β1-induced reduction of AmsIsc was alleviated in the N-terminal truncated Smad4-overexpressed cells. Conclusion. It appears that the N-terminus region of Smad4 is indispensable in Smad4-mediated inhibition of the transepithelial sodium transport. TGF-β1 may decrease the ENaC functionality via a Smad4-dependent pathway.
- Subjects
CELLULAR mechanics; GROWTH factors; CYTOKINES; MESSENGER RNA
- Publication
Nephrology Dialysis Transplantation, 2008, Vol 23, Issue 4, p1126
- ISSN
0931-0509
- Publication type
Article