Table of Contents
To view the fulltext, log-in or choose pay-per-view options:
Get Access

Endothelin-1 Induces NF-κB via Two Independent Pathways in Human Renal Tubular Epithelial Cells

Gerstung M.a · Roth T.a · Dienes H.-P.a · Licht C.b · Fries J.W.U.a
aDepartment of Pathology, University of Cologne, Cologne, Germany, and bDivision of Nephrology, Hospital for Sick Children, Toronto, Ont., Canada Am J Nephrol 2007;27:294–300 (DOI:10.1159/000101999)

Abstract

Background: Endothelin-1 (ET-1) is a major transcriptional activator of renal proximal tubule cells acting in an autocrine and paracrine manner. In animal studies, ET-1 has been implicated in progressive renal interstitial fibrosis by promoting gene expression, possibly via the inflammatory NF-ĸB signal pathway. While ET-1-dependent mechanisms of signal transduction have been studied mainly in tumor cell lines, we analyzed the mechanism of ET-1-induced, NF-ĸB-mediated target gene activation in proximal tubule cells. Methods: Human renal proximal tubule cells were stimulated with ET-1 and gene expression analyzed by protein microarray, Western blot, non-radioactive electromobility shift assay, and quantitative real-time polymerase chain reaction. Results: Activation of NF-ĸB occurs only via an ET-1-specific type A receptor (not type B as in animals). Induction can be blocked by bosentan, and endothelin-A but not endothelin-B receptor-specific antagonists. Protein microarray screening shows activation of two independent cascades (via the endothelin-A receptor, or via diacylglycerol) leading to NF-ĸB induction. The independent induction is also reflected by target gene expression such as the vascular cell adhesion molecule-1, interleukin-6, and fractalkine at different time points. Conclusion: Thus prohibiting ET-1-mediated gene transcription necessitates blocking of NF-ĸB and diacylglycerol signal transduction in proximal tubule cells.

 

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50