title: MG53-mediated cell membrane repair protects against acute kidney injury.
abstract: 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.
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Pu
authors: P
authors: Duann
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Haichang
authors: H
authors: Li
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Peihui
authors: P
authors: Lin
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Tao
authors: T
authors: Tan
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing 400042, China.
authors: Zhen
authors: Z
authors: Wang
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing 400042, China.
authors: Ken
authors: K
authors: Chen
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Xinyu
authors: X
authors: Zhou
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Kristyn
authors: K
authors: Gumpper
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Hua
authors: H
authors: Zhu
authors: Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors: Thomas
authors: T
authors: Ludwig
authors: Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.|Department of Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Peter J
authors: PJ
authors: Mohler
authors: Department of Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Brad
authors: B
authors: Rovin
authors: Department of Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: William T
authors: WT
authors: Abraham
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing 400042, China.
authors: Chunyu
authors: C
authors: Zeng
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.|Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors: Jianjie
authors: J
authors: Ma
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002945:Cisplatin / Q000009:adverse effects; D004285:Dogs; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D000070584:Tripartite Motif Proteins
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D011994:Recombinant Proteins; C558399:TRIM72 protein, human; D000070584:Tripartite Motif Proteins; D002945:Cisplatin