{"doi":"10.1016/j.kint.2021.09.027","title":"The cell membrane repair protein MG53 modulates transcription factor NF-κB signaling to control kidney fibrosis","abstract":"Kidney fibrosis is associated with the progression of acute kidney injury to chronic kidney disease. MG53, a cell membrane repair protein, has been shown to protect against injury to kidney epithelial cells and acute kidney injury. Here, we evaluated the role of MG53 in modulation of kidney fibrosis in aging mice and in mice with unilateral ureteral obstruction (UUO) a known model of progressive kidney fibrosis. Mice with ablation of MG53 developed more interstitial fibrosis with age than MG53-intact mice of the same age. Similarly, in the absence of MG53, kidney fibrosis was exaggerated compared to mice with intact MG53 in the obstructed kidney compared to the contralateral unobstructed kidney or the kidneys of sham operated mice. The ureteral obstructed kidneys from MG53 deficient mice also showed significantly more inflammation than ureteral obstructed kidneys from MG53 intact mice. In vitro experiments demonstrated that MG53 could enter the nuclei of proximal tubular epithelial cells and directly interact with the p65 component of transcription factor NF-κB, providing a possible explanation of enhanced inflammation in the absence of MG53. To test this, enhanced MG53 expression through engineered cells or direct recombinant protein delivery was given to mice subject to UUO. This reduced NF-κB activation and inflammation and attenuated kidney fibrosis. Thus, MG53 may have a therapeutic role in treating chronic kidney inflammation and thereby provide protection against fibrosis that leads to the chronic kidney disease phenotype. Kidney fibrosis is associated with the progression of acute kidney injury to chronic kidney disease. MG53, a cell membrane repair protein, has been shown to protect against injury to kidney epithelial cells and acute kidney injury. Here, we evaluated the role of MG53 in modulation of kidney fibrosis in aging mice and in mice with unilateral ureteral obstruction (UUO) a known model of progressive kidney fibrosis. Mice with ablation of MG53 developed more interstitial fibrosis with age than MG53-intact mice of the same age. Similarly, in the absence of MG53, kidney fibrosis was exaggerated compared to mice with intact MG53 in the obstructed kidney compared to the contralateral unobstructed kidney or the kidneys of sham operated mice. The ureteral obstructed kidneys from MG53 deficient mice also showed significantly more inflammation than ureteral obstructed kidneys from MG53 intact mice. In vitro experiments demonstrated that MG53 could enter the nuclei of proximal tubular epithelial cells and directly interact with the p65 component of transcription factor NF-κB, providing a possible explanation of enhanced inflammation in the absence of MG53. To test this, enhanced MG53 expression through engineered cells or direct recombinant protein delivery was given to mice subject to UUO. This reduced NF-κB activation and inflammation and attenuated kidney fibrosis. Thus, MG53 may have a therapeutic role in treating chronic kidney inflammation and thereby provide protection against fibrosis that leads to the chronic kidney disease phenotype. Translational StatementChronic inflammation leads to fibrotic remodeling that may also underlie the transition from acute kidney injury to chronic kidney disease. Activation of the proinflammatory transcription factor nuclear factor κB (NF-κB) is involved in the pathogenesis of kidney inflammation. Here, we provide evidence that MG53, a previously identified cell membrane repair protein, directly interacts with NF-κB and reduces its transcriptional activity. Concomitantly, exogenously administered MG53 can decrease fibrotic remodeling of the inflamed kidney. These findings point to a protective interplay between MG53 and NF-κB to attenuate the development of inflammation-mediated kidney fibrosis. Pharmacologic administration of MG53 might be a promising approach for the treatment of progressive kidney fibrosis. Chronic inflammation leads to fibrotic remodeling that may also u","journal":"Kidney International","year":2021,"id":159904,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":671926,"name":"Pu Duann","orcid":"0000-0002-0145-3058","position":1,"is_corresponding":false},{"id":649368,"name":"Zhong‐Guang Li","orcid":"0000-0002-6161-0377","position":2,"is_corresponding":false},{"id":649367,"name":"Xinyu Zhou","orcid":"0000-0002-1606-5816","position":3,"is_corresponding":false},{"id":341623,"name":"Jianjie Ma","orcid":"0000-0003-3865-6112","position":4,"is_corresponding":false},{"id":284163,"name":"Brad H. Rovin","orcid":"0000-0001-5639-0210","position":5,"is_corresponding":false},{"id":341621,"name":"Pei‐Hui Lin","orcid":"0000-0002-3894-5099","position":6,"is_corresponding":false},{"id":341622,"name":"Haichang Li","orcid":"0000-0001-9784-6480","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:44:43.908634Z","pmid":"34757120","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}