Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway

Frontiers in Pharmacology

Cong Zou¹  Shuangyang Zhang²  Wenlin Chen³  Xiaoqing Xi³  Honglin Hu³  Renrui Kuang³  Zhenfeng Ye³  Yawei Huang³ 

[1] Department of Endocrinology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China;Department of Urology, The Hospital of Wuchang, Wuhan, China;Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, China;

关键词: pioglitazone;    renal ischemia reperfusion injury;    peroxisome proliferators-activated receptor-γ;    autophagy;    cell apoptosis;   

DOI  :  10.3389/fphar.2018.00851

来源: DOAJ

【 摘 要 】

Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the renoprotective effects of pioglitazone is still unclear. In this study, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renoprotection by pioglitazone in IRI. To investigate whether pioglitazone protects renal cells from IRI, an in vivo renal IRI model was used. Cell apoptosis in the kidneys was determined by TUNEL staining. Western blotting was used to determine the expression of AMPK, autophagy-related proteins, and caspase-3/8 proteins in the kidneys. In a rat model of IRI, pioglitazone decreased the increased serum creatinine and urea nitrogen, improved renal histological score, and decreased the cell injury. Pioglitazone also increased AMPK phosphorylation, inhibited p62 and cleaved caspase-3/8 proteins, and activated autophagy-related proteins LC3 II and Beclin-1 in the kidneys of IRI rats. Moreover, GW9662, as a selective inhibitor of PPAR-γ, inhibited the protective effects of pioglitazone. These results suggest that pioglitazone exerts its protective effects in renal IRI via activation of an AMPK-regulated autophagy signaling pathway.

【 授权许可】

Unknown