The peroxisome proliferator-activated receptor-α agonist, BAY PP1, attenuates renal fibrosis in rats

Peter Boor, Peter Celec, Ina V. Martin, Luigi Villa, Július Hodosy, Kristína Klenovicsová, Ciro Esposito, Stefan Schäfer, Barbara Albrecht-Küpper, Tammo Ostendorf, August Heidland, Katarína Šebeková

Research output: Contribution to journalArticle

Abstract

Recent studies have shown renoprotective effects of the peroxisome proliferator-activated receptor-α (PPAR-α), but its role in kidney fibrosis is unknown. In order to gain insight into this, we examined the effect of a novel PPAR-α agonist, BAY PP1, in two rat models of renal fibrosis: unilateral ureteral obstruction and the 5/6 nephrectomy. In healthy animals, PPAR-α was expressed in tubular but not in interstitial cells. Upon induction of fibrosis, PPAR-α was significantly downregulated, and treatment with BAY PP1 significantly restored its expression. During ureteral obstruction, treatment with BAY PP1 significantly reduced tubulointerstitial fibrosis, proliferation of interstitial fibroblasts, and TGF-Β 1 expression. Treatment with a less potent PPAR-α agonist, fenofibrate, had no effects. Treatment with BAY PP1, initiated in established disease in the 5/6 nephrectomy, halted the decline of renal function and significantly ameliorated renal fibrosis. In vitro, BAY PP1 had no direct effect on renal fibroblasts but reduced collagen, fibronectin, and TGF-Β 1 expression in tubular cells. Conditioned media of BAY PP1-treated tubular cells reduced fibroblast proliferation. Thus, renal fibrosis is characterized by a reduction of PPAR-α expression, and treatment with BAY PP1 restores PPAR-α expression and ameliorates renal fibrosis by modulating the cross-talk between tubular cells and fibroblasts. Hence, potent PPAR-α agonists might be useful in the treatment of renal fibrosis.

Original languageEnglish
Pages (from-to)1182-1197
Number of pages16
JournalKidney International
Volume80
Issue number11
DOIs
Publication statusPublished - Dec 2011

ASJC Scopus subject areas

  • Nephrology

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    Boor, P., Celec, P., Martin, I. V., Villa, L., Hodosy, J., Klenovicsová, K., Esposito, C., Schäfer, S., Albrecht-Küpper, B., Ostendorf, T., Heidland, A., & Šebeková, K. (2011). The peroxisome proliferator-activated receptor-α agonist, BAY PP1, attenuates renal fibrosis in rats. Kidney International, 80(11), 1182-1197. https://doi.org/10.1038/ki.2011.254