MG53 protects against contrast-induced acute kidney injury by reducing cell membrane damage and apoptosis

Chao Liu1,2, Yun-hui Hu1,2, Yu Han1,2, Yong-bin Wang1,2, Yan Zhang1,2, Xiao-qun Zhang1,2, Duo-fen He1,2, Hong-mei Ren1,2, Yu-kai Liu1,2, Hong-yong Wang1,2, Tao Tan3, Pei-hui Lin3, Hai-chang Li3, Brad H. Rovin4, Jian-jie Ma3, Chun-yu Zeng1,2,5
1 Department of Cardiology, Daping Hospital, Army Medical University, Chongqing 400042, China
2 Chongqing Institute of Cardiology & Chongqing Key Laboratory of Hypertension Research, Chongqing 400042, China
3 Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
4 Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
5 Department of Cardiology, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou 350001, China
Correspondence to: Yu Han:, Chun-yu Zeng:,
DOI: 10.1038/s41401-020-0420-8
Received: 15 January 2020
Accepted: 15 April 2020
Advance online: 18 May 2020


Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 μg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.
Keywords: contrast media; renal tubular epithelium; MG53 protein; cell membrane repair; acute kidney injury; apoptosis

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