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

• Published in: Acta pharmacologica Sinica Vol. 41; no. 11; pp. 1457 - 1464
• Main Authors: Liu, Chao, Hu, Yun-hui, Han, Yu, Wang, Yong-bin, Zhang, Yan, Zhang, Xiao-qun, He, Duo-fen, Ren, Hong-mei, Liu, Yu-kai, Wang, Hong-yong, Tan, Tao, Lin, Pei-hui, Li, Hai-chang, Rovin, Brad H., Ma, Jian-jie, Zeng, Chun-yu
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.11.2020; Nature Publishing Group
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - pathology; Acute Kidney Injury - prevention & control; Animals; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cell death; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell membranes; Contrast media; Creatinine; Cytotoxicity; Epithelial Cells; Female; Humans; Immunology; Internal Medicine; Iohexol - analogs & derivatives; Kidney - pathology; Kidney Tubules, Proximal - cytology; Kidneys; Male; Medical Microbiology; Pharmacology/Toxicology; Phosphatidylserine; Phosphatidylserines - metabolism; Protective Agents - metabolism; Protective Agents - therapeutic use; Rats, Inbred WKY; Rats, Sprague-Dawley; Recombinant Proteins - metabolism; Recombinant Proteins - therapeutic use; Tripartite Motif Proteins - metabolism; Tripartite Motif Proteins - therapeutic use; Urea; Vaccine; cell membrane repair; apoptosis; acute kidney injury; MG53 protein; renal tubular epithelium; contrast media
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/s41401-020-0420-8

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.