| First Author | Li S | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 5 | Pages | F618-27 |
| PubMed ID | 23804447 | Mgi Jnum | J:200941 |
| Mgi Id | MGI:5510292 | Doi | 10.1152/ajprenal.00309.2013 |
| Citation | Li S, et al. (2013) Proximal tubule PPARalpha attenuates renal fibrosis and inflammation caused by unilateral ureteral obstruction. Am J Physiol Renal Physiol 305(5):F618-27 |
| abstractText | We examined the effects of increased expression of proximal tubule peroxisome proliferator-activated receptor (PPAR)alpha in a mouse model of renal fibrosis. After 5 days of unilateral ureteral obstruction (UUO), PPARalpha expression was significantly reduced in kidney tissue of wild-type mice but this downregulation was attenuated in proximal tubules of PPARalpha transgenic (Tg) mice. When compared with wild-type mice subjected to UUO, PPARalpha Tg mice had reduced mRNA and protein expression of proximal tubule transforming growth factor (TGF)-beta1, with reduced production of extracellular matrix proteins including collagen 1, fibronectin, alpha-smooth muscle actin, and reduced tubulointerstitial fibrosis. UUO-mediated increased expression of microRNA 21 in kidney tissue was also reduced in PPARalpha Tg mice. Overexpression of PPARalpha in cultured proximal tubular cells by adenoviral transduction reduced aristolochic acid-mediated increased production of TGF-beta, demonstrating PPARalpha signaling reduces epithelial TGF-beta production. Flow cytometry studies of dissociated whole kidneys demonstrated reduced macrophage infiltration to kidney tissue in PPARalpha Tg mice after UUO. Increased expression of proinflammatory cytokines including IL-1beta, IL-6, and TNF-alpha in wild-type mice was also significantly reduced in kidney tissue of PPARalpha Tg mice. In contrast, the expression of anti-inflammatory cytokines IL-10 and arginase-1 was significantly increased in kidney tissue of PPARalpha Tg mice when compared with wild-type mice subjected to UUO. Our studies demonstrate several mechanisms by which preserved expression of proximal tubule PPARalpha reduces tubulointerstitial fibrosis and inflammation associated with obstructive uropathy. |
