Estrogen-Related Receptor α Mediates Puromycin Aminonucleoside-induced Mesangial Cell apoptosis and Inflammatory Injury.

Estrogen-Related Receptor α Mediates Puromycin Aminonucleoside-induced Mesangial Cell apoptosis and Inflammatory Injury. Am J Physiol Renal Physiol. 2019 Jan 30;: Authors: Gong W, Song J, Chen X, Li S, Yu J, Xia W, Ding G, Zhang Y, Jia Z, Zhang A, Huang S Abstract Glomerular diseases are the leading causes of chronic kidney disease and mesangial cells (MCs) were demonstrated to be involved in the pathogenesis. Puromycin aminonucleoside (PAN) is a nephrotoxic drug that induced glomerular injury with elusive mechanisms. The present study is undertaken to investigate the role of PAN in MC apoptosis, as well as the underlying mechanism. Here we found that PAN induced MC apoptosis accompanied by the declined cell viability and enhanced inflammatory response. The apoptosis was further evidenced by the increments of BAX and Caspase-3 expression. In line with the apoptotic response in MCs following PAN treatment, we also found a remarkable induction of estrogen-related receptor α (ERRα), an orphan nuclear receptor, at both mRNA and protein levels. Interestingly, ERRα silencing by a siRNA approach resulted in an attenuation of apoptosis and inflammatory response caused by PAN. More importantly, overexpression of ERRα in MCs significantly triggered MC apoptosis in line with increased BAX and Caspase-3 expression. In PAN-treated MCs, ERRα overexpression further aggravated PAN-induced apoptosis. In agreement with the in vitro study, we als...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research