Xiu-Juan Liu1, Quan Hong, Zhen Wang, Yan-Yan Yu, Xin Zou, Li-Hong Xu. 1. Department of Nephrology, The 94th Hospital of Chinese People's Liberation Army, The Changcheng Affiliated Hospital of Nanchang University, Nanchang, China.
Abstract
BACKGROUND: Acute kidney injury (AKI) is traditionally described as a condition leading to rapid damage to kidney function, eventually becoming a significant healthcare concern with a high mortality rate. Autophagy deficiency in the tubular epithelial cells is the main cause of AKI; however, the underlying molecular mechanism remains to be defined. MicroRNAs (miRNAs) are related to autophagy in many diseases. This study was aimed at investigating the relationship between miRNA expression and autophagic activity in the pathogenesis of AKI. METHODS: A mouse model of AKI was produced by ischemia reperfusion (I/R). The expressions of microRNA-34a (miR-34a) and the autophagy-related protein LC3 II/I and p62 were determined in renal tissues and the tubular epithelial cells (RTECs). Moreover, the autophagic activity was investigated after miR-34a overexpression and inhibition. Additionally, the effect of miR-34a on its target gene in regulating autophagic activity in RTECs was also investigated. RESULTS: I/R suppressed the autophagic activity and increased the expression of miR-34a in renal tissues. The in vitro data showed that the upregulation of miR-34a suppressed, whereas the inhibition of miR-34a promoted, autophagy in RTECs. Moreover, miR-34a could directly bind to Atg4B 3'-untranslated region. In addition, the knockdown of Atg4B expression inhibited the autophagic activity in RTECs. CONCLUSION: This study indicated that miR-34a might regulate the autophagic activity and can cause injury in I/R RTECs via targeting Atg4B.
BACKGROUND:Acute kidney injury (AKI) is traditionally described as a condition leading to rapid damage to kidney function, eventually becoming a significant healthcare concern with a high mortality rate. Autophagy deficiency in the tubular epithelial cells is the main cause of AKI; however, the underlying molecular mechanism remains to be defined. MicroRNAs (miRNAs) are related to autophagy in many diseases. This study was aimed at investigating the relationship between miRNA expression and autophagic activity in the pathogenesis of AKI. METHODS: A mouse model of AKI was produced by ischemia reperfusion (I/R). The expressions of microRNA-34a (miR-34a) and the autophagy-related protein LC3 II/I and p62 were determined in renal tissues and the tubular epithelial cells (RTECs). Moreover, the autophagic activity was investigated after miR-34a overexpression and inhibition. Additionally, the effect of miR-34a on its target gene in regulating autophagic activity in RTECs was also investigated. RESULTS: I/R suppressed the autophagic activity and increased the expression of miR-34a in renal tissues. The in vitro data showed that the upregulation of miR-34a suppressed, whereas the inhibition of miR-34a promoted, autophagy in RTECs. Moreover, miR-34a could directly bind to Atg4B 3'-untranslated region. In addition, the knockdown of Atg4B expression inhibited the autophagic activity in RTECs. CONCLUSION: This study indicated that miR-34a might regulate the autophagic activity and can cause injury in I/R RTECs via targeting Atg4B.