Transforming growth factor-β1 decreases epithelial sodium channel functionality in renal collecting duct cells via a Smad4-dependent pathway

Chiz Tzung Chang, Cheng Chieh Hung, Yung Chang Chen, Tzung Hai Yen, Mai Szu Wu, Chih Wei Yang, Aled Phillips, Ya Chung Tian

研究成果: 雜誌貢獻文章

14 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1126-1134
頁數9
期刊Nephrology Dialysis Transplantation
23
發行號4
DOIs
出版狀態已發佈 - 四月 2008
對外發佈Yes

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Medicine(all)

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