title: Protective effects of adiponectin against renal ischemia-reperfusion injury via prostacyclin-PPARα-heme oxygenase-1 signaling pathway.
abstract: Adiponectin (APN), a circulating adipose-derived hormone that regulates inflammation and energy metabolism, has beneficial effects on the cardiovascular disorders. Serum APN levels are lower in patients with coronary artery disease and higher in patients with chronic kidney disease. However, the precise role of APN in acute reno-vascular disease is not clear. Results of the present study show that serum APN concentration decreased after renal ischemia reperfusion (I/R) injury in mice. In addition, I/R-induced renal dysfunction (elevated serum creatinine and urea levels), inflammation (number of infiltrating neutrophils, myeloperoxidase activity), and apoptotic responses (apoptotic cell number and caspase-3 activation) were attenuated in APN-treated compared to control mice. Molecular and biochemical analysis revealed that APN up-regulates heme oxygenase-1 (HO-1) via peroxisome-proliferator-activated-receptor-α (PPARα) dependent pathway which is mediated through the enhancement of COX-2 and 6-keto PGF1α expression. Chromatin immune-precipitation assay demonstrated that APN increases the binding activity of PPARα to PPRE region of HO-1 promoter. Furthermore, APN induced HO-1 expression was only found in wild-type but not in PPARα gene deleted mice. This provides in vivo evidence that APN mediated HO-1 expression depends on PPARα regulation. In conclusion, our results provide a novel APN mediated prostacyclin-PPARα-HO-1 signaling pathway in protecting renal I/R injury.
authors.affiliation: Department of Medical Research, Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Lian
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Chen
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Lai
authors.forename: Hsiao-Fen
authors.initials: HF
authors.lastname: Li
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Lan
authors.forename: Winston Teng-Kuei
authors.initials: WT
authors.lastname: Cheng
authors.forename: Heng
authors.initials: H
authors.lastname: Lin
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000172:deficiency / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D052242:Adiponectin; D047493:PPAR alpha; D011464:Epoprostenol; D051547:Heme Oxygenase-1