CREB1 protects against the renal injury in a rat model of kidney stone disease and calcium oxalate monohydrate crystals-induced injury in NRK-52E cells

Abstract

Kidney stone disease (KSD) is a common urinary disease with increasing prevalence worldwide. In this study, we investigated the effect of cyclic AMP responsive element binding protein (CREB) 1 in a KSD model of rat and calcium oxalate monohydrate (COM) crystals-treated NRK-52E cells. Rats were pretreated with lentivirus (LV)-CREB1 vector or LV-control vector and administrated with ethylene glycol + ammonium chloride to induce KSD. It was found that CREB1 was activated in the renal tissue of non-treated KSD rats. Pretreating with LV-CREB1 vector significantly enhanced CREB1 expression in KSD rats. Biochemical analysis for serum and urine showed that upregulation of CREB1 could improve the renal function of KSD rats. Histological analysis confirmed that upregulation of CREB1 alleviated the renal injury in KSD rats. Moreover, the upregulation of CREB1 suppressed the apoptosis in renal tissue of KSD rats through regulating apoptosis-associated proteins. Further study showed that the upregulation of CREB1 could attenuate the oxidative stress in KSD rats as well. More interestingly, the upregulation of CREB1 enhanced the activity of complex I and complex III and the expression of mitochondrial cytochrome c, implicating the effect of CREB1 on improving mitochondrial function in KSD rats. In vitro study confirmed that upregulation of CREB1 inhibited the apoptosis and oxidative stress, while improved the mitochondrial function of NRK-52E cells treated with COM crystals, demonstrating the protective effect of CREB1 on COM crystals-induced renal epithelial cell injury. Therefore, CREB1 might be served as a promising target in the prophylaxis and treatment of KSD.