PPARα activation upregulates nephrin expression in human embryonic kidney epithelial cells and podocytes by a dual mechanism

S Ren, C Xin, KF Beck, MA Saleem, PW Mathieson, H Pavenstadt, J Pfeilschifter, A Huwiler

Research output: Contribution to journalArticle (Academic Journal)peer-review

34 Citations (Scopus)

Abstract

Nephrin is an important member of the glomerular ultrafiltration complex and changes in its expression are associated with severe proteinuria. In this study, we show that synthetic PPAR[alpha] agonists, but not PPAR[gamma] agonists, stimulate an increased nephrin mRNA and protein expression in cultures of human podocytes and A293 human embryonic kidney epithelial cells which are blocked by the PPAR[alpha] antagonist RU486. Furthermore, the PPAR[alpha] agonists have an additive effect on the interleukin-1[beta] (IL-1[beta])-induced nephrin upregulation. Luciferase-reporter assays reveal that human nephrin promoter activity is stimulated by the PPAR[alpha] agonists. Neither IL-1[beta] nor TNF[alpha] alone has an effect on nephrin promoter activity suggesting that additional posttranscriptional regulatory events might be operative. The role of nephrin mRNA stability regulation was evaluated in cells treated with actinomycin D to stop further RNA transcription. In the presence of PPAR[alpha] agonists, IL-1[beta] or TNF[alpha], the decay of nephrin mRNA was drastically reduced thus arguing for an additional posttranscriptional mode of action. In summary, these data show that PPAR[alpha] activation causes an increased nephrin expression by a dual action, on the one hand by stimulating nephrin promoter activity and on the other hand by reducing nephrin mRNA degradation. These findings may have importance for treatment strategies of renal diseases affecting the expression of nephrin and subsequently the proper action of the glomerular filtration apparatus.
Translated title of the contributionPPARα activation upregulates nephrin expression in human embryonic kidney epithelial cells and podocytes by a dual mechanism
Original languageEnglish
Pages (from-to)1818 - 1824
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume338 (4)
DOIs
Publication statusPublished - Dec 2006

Bibliographical note

Publisher: Elsevier

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