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

被引：45

作者：

Boor, Peter ^{[1
,2
,3
]}

Celec, Peter ^{[4
,5
,6
]}

Martin, Ina V. ^{[1
]}

Villa, Luigi ^{[1
,7
]}

Hodosy, Julius ^{[4
,5
,6
]}

Klenovicsova, Kristina ^{[3
]}

Esposito, Ciro ^{[7
]}

Schaefer, Stefan ^{[8
]}

Albrecht-Kuepper, Barbara ^{[8
]}

Ostendorf, Tammo ^{[1
]}

Heidland, August ^{[9
]}

Sebekova, Katarina ^{[4
,5
,6
]}

机构：

[1] Rhein Westfal TH Aachen, Div Nephrol, Aachen, Germany

[2] Rhein Westfal TH Aachen, Inst Pathol, Aachen, Germany

[3] Slovak Med Univ, Res Base, Dept Clin & Expt Pharmacotherapy, Bratislava, Slovakia

[4] Comenius Univ, Inst Mol Biomed, Bratislava, Slovakia

[5] Comenius Univ, Inst Pathophysiol, Bratislava, Slovakia

[6] Comenius Univ, Dept Mol Biol, Bratislava, Slovakia

[7] Univ Pavia, Unit Nephrol Dialysis & Transplantat, I-27100 Pavia, Italy

[8] Bayer Schering Pharma AG, Cardiol Res, Wuppertal, Germany

[9] Univ Wurzburg, Dept Internal Med, Wurzburg, Germany

来源：

KIDNEY INTERNATIONAL | 2011年 / 80卷 / 11期

关键词：

extracellular matrix; fenofibrate; fibroblasts; kidney scarring; peroxisome proliferator-activated receptor (PPAR); proliferation; PPAR-ALPHA; OBSTRUCTIVE NEPHROPATHY; FENOFIBRATE; EXPRESSION; GAMMA; ACCUMULATION; INFLAMMATION; REDUCTION; PRESSURE; PROTECTS;

D O I：

10.1038/ki.2011.254

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Recent studies have shown renoprotective effects of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), but its role in kidney fibrosis is unknown. In order to gain insight into this, we examined the effect of a novel PPAR-alpha agonist, BAY PP1, in two rat models of renal fibrosis: unilateral ureteral obstruction and the 5/6 nephrectomy. In healthy animals, PPAR-alpha was expressed in tubular but not in interstitial cells. Upon induction of fibrosis, PPAR-alpha 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-beta(1) expression. Treatment with a less potent PPAR-alpha 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-beta(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-alpha expression, and treatment with BAY PP1 restores PPAR-alpha expression and ameliorates renal fibrosis by modulating the cross-talk between tubular cells and fibroblasts. Hence, potent PPAR-alpha agonists might be useful in the treatment of renal fibrosis. Kidney International (2011) 80, 1182-1197; doi:10.1038/ki.2011.254; published online 3 August 2011

引用

页码：1182 / 1197

页数：16

共 32 条

[11] Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans [J].