Jun Xu1, Liang Ma2, Ping Fu3. 1. Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China; Division of Nephrology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550014,China. 2. Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China. Electronic address: Liang_m@scu.edu.cn. 3. Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China. Electronic address: fupinghx@scu.edu.cn.
Abstract
BACKGROUNDS: Contrast-induced acute kidney injury (CIAKI) is the third most common cause of hospital-acquired AKI. It has been demonstrated that microRNA-30c (miR-30c) was upregulated in the CIAKI. However, the underlying mechanism remain unclear. METHODS: The CIAKI was induced in miniature pig. The expression profile of miR-30c in the kidney was evaluated by qPCR. The pathways regulated by miR-30c was identified by qPCR and western blot on renal tubular epithelial cells isolated from miniature pig. Finally, the potential therapeutic application of targeting miR-30c was assessed in the pig model of CIAKI. RESULTS: The miR-30c was up-regulated in miniature pig with CIAKI. The miR-30c suppressed cell apoptosis, expression of NLRP3, the secretion of IL-1β and caspase-1 p10 on renal cells stimulated by iohexol in vitro. In the pig model, miR-30c inhibited the CIAKI development. CONCLUSION: Our data demonstrated that the miR-30c induced by CIAKI could suppress cell apoptosis and kidney injury via targeting NLRP3. Therefore, targeting miR-30c might be a novel therapeutic candidate for CIAKI treatment and prevention.
BACKGROUNDS: Contrast-induced acute kidney injury (CIAKI) is the third most common cause of hospital-acquired AKI. It has been demonstrated that microRNA-30c (miR-30c) was upregulated in the CIAKI. However, the underlying mechanism remain unclear. METHODS: The CIAKI was induced in miniature pig. The expression profile of miR-30c in the kidney was evaluated by qPCR. The pathways regulated by miR-30c was identified by qPCR and western blot on renal tubular epithelial cells isolated from miniature pig. Finally, the potential therapeutic application of targeting miR-30c was assessed in the pig model of CIAKI. RESULTS: The miR-30c was up-regulated in miniature pig with CIAKI. The miR-30c suppressed cell apoptosis, expression of NLRP3, the secretion of IL-1β and caspase-1 p10 on renal cells stimulated by iohexol in vitro. In the pig model, miR-30c inhibited the CIAKI development. CONCLUSION: Our data demonstrated that the miR-30c induced by CIAKI could suppress cell apoptosis and kidney injury via targeting NLRP3. Therefore, targeting miR-30c might be a novel therapeutic candidate for CIAKI treatment and prevention.
Authors: Balamurugan Packialakshmi; Ian J Stewart; David M Burmeister; Kevin K Chung; Xiaoming Zhou Journal: Ren Fail Date: 2020-11 Impact factor: 2.606