Research ArticleKidney Disease

MG53-mediated cell membrane repair protects against acute kidney injury

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Science Translational Medicine  18 Mar 2015:
Vol. 7, Issue 279, pp. 279ra36
DOI: 10.1126/scitranslmed.3010755

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A molecular bandage for kidney injury

MG53 is a protein that is primarily expressed in muscles and helps protect muscle cells from damage. Now, Duann et al. have shown that MG53 performs a similar function in the kidney as well. The authors evaluated the role of MG53 in mouse models of kidney injury induced by ischemia and reperfusion, as well as by cisplatin, a highly nephrotoxic chemotherapy drug. In each case, recombinant MG53 could be given intravenously, and the authors found that it bound to the sites of injury on kidney cells and protected them from further damage and death. MG53 treatment did not interfere with the effectiveness of cisplatin against cancer cells, suggesting that MG53 may be useful for protecting patients’ kidneys during chemotherapy.


Injury to the renal proximal tubular epithelium (PTE) represents the underlying consequence of acute kidney injury (AKI) after exposure to various stressors, including nephrotoxins and ischemia/reperfusion (I/R). Although the kidney has the ability to repair itself after mild injury, insufficient repair of PTE cells may trigger inflammatory and fibrotic responses, leading to chronic renal failure. We report that MG53, a member of the TRIM family of proteins, participates in repair of injured PTE cells and protects against the development of AKI. We show that MG53 translocates to acute injury sites on PTE cells and forms a repair patch. Ablation of MG53 leads to defective membrane repair. MG53-deficient mice develop pronounced tubulointerstitial injury and increased susceptibility to I/R-induced AKI compared to wild-type mice. Recombinant human MG53 (rhMG53) protein can target injury sites on PTE cells to facilitate repair after I/R injury or nephrotoxin exposure. Moreover, in animal studies, intravenous delivery of rhMG53 ameliorates cisplatin-induced AKI without affecting the tumor suppressor efficacy of cisplatin. These findings identify MG53 as a vital component of reno-protection, and targeting MG53-mediated repair of PTE cells represents a potential approach to prevention and treatment of AKI.

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