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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1126-1134
Number of pages9
JournalNephrology Dialysis Transplantation
Volume23
Issue number4
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

    Fingerprint

Keywords

  • Cortical collecting duct
  • Epithelial sodium channel
  • Short circuit current
  • Smad signalling pathway
  • TGF-β1

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Medicine(all)

Cite this