过氧化物酶体增殖物激活受体γ共激活剂1α可减轻线粒体功能障碍并保护足细胞免受醛固酮诱导性损伤

Zhang, A.; Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210029, Jiangsu Province, China; email:zhaihua@njmu.edu.cn

Glomerular podocytes are highly specialized epithelial cells whose injury in glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an early event in podocyte injury, we tested whether a major regulator of oxidative metabolism and mitochondrial function, the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), affects podocyte damage. Aldosterone-induced injury decreased PGC-1α expression, and induced mitochondrial and podocyte damage in dose-and time-dependent manners. The suppression of endogenous PGC-1α by RNAi caused podocyte mitochondrial damage and apoptosis while its increase by infection with an adenoviral vector prevented aldosterone-induced mitochondrial malfunction and inhibited injury. Overexpression of the silent mating type information regulation 2 homolog 1, a gene upstream of PGC-1α, prevented aldosterone-induced mitochondrial damage and podocyte injury by upregulating PGC-1α at both the transcriptional and post-translational levels. Resveratrol, a SIRT1 activator, attenuated aldosterone-induced mitochondrial malfunction and podocyte injury in vitro and in aldosterone-infused mice in vivo. Hence, endogenous PGC-1α may be important for maintenance of mitochondrial function in podocytes under normal conditions. Activators of SIRT1, such as resveratol, may be therapeutically useful in glomerular diseases to promote and maintain PGC-1α expression and, consequently, podocyte integrity. © 2012 International Society of Nephrology.

Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210029, Jiangsu Province, China