TY - JOUR
T1 - Protective effects of adiponectin against renal ischemia-reperfusion injury via prostacyclin-PPARα-Heme oxygenase-1 signaling pathway
AU - Cheng, Ching Feng
AU - Lian, Wei Shiung
AU - Chen, Sung Ho
AU - Lai, Pei Fen
AU - Li, Hsiao Fen
AU - Lan, Yi Fan
AU - Cheng, Winston Teng Kuei
AU - Lin, Heng
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80054881208&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054881208&partnerID=8YFLogxK
U2 - 10.1002/jcp.22726
DO - 10.1002/jcp.22726
M3 - Article
C2 - 21412771
AN - SCOPUS:80054881208
SN - 0021-9541
VL - 227
SP - 239
EP - 249
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 1
ER -