{"doi":"10.1016/j.molmet.2023.101680","title":"Endotrophin neutralization through targeted antibody treatment protects from renal fibrosis in a podocyte ablation model","abstract":"OBJECTIVE: Renal fibrosis is a hallmark for chronic kidney disease (CKD), and often leads to end stage renal disease (ESRD). However, limited interventions are available clinically to ameliorate or reverse renal fibrosis. METHODS: Herein, we evaluated whether blockade of endotrophin through neutralizing antibodies protects from renal fibrosis in the podocyte insult model (the \"POD-ATTAC\" mouse). We determined the therapeutic effects of endotrophin targeted antibody through assessing renal function, renal inflammation and fibrosis at histological and transcriptional levels, and podocyte regeneration. RESULTS: We demonstrated that neutralizing endotrophin antibody treatment significantly ameliorates renal fibrosis at the transcriptional, morphological, and functional levels. In the antibody treatment group, expression of pro-inflammatory and pro-fibrotic genes was significantly reduced, normal renal structures were restored, collagen deposition was decreased, and proteinuria and renal function were improved. We further performed a lineage tracing study confirming that podocytes regenerate as de novo podocytes upon injury and loss, and blockade of endotrophin efficiently enhances podocyte-specific marker expressions. CONCLUSION: Combined, we provide pre-clinical evidence supporting neutralizing endotrophin as a promising therapy for intervening with renal fibrosis in CKD, and potentially in other chronic fibro-inflammatory diseases.","journal":"Molecular Metabolism","year":2023,"id":337948,"datarank":0.6013956576548525,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.16783989397042778,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.16783989397042778,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":11,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244930,"name":"Wei Xiong","orcid":"0000-0002-8087-5047","position":1,"is_corresponding":false},{"id":617454,"name":"Shiuhwei Chen","orcid":null,"position":2,"is_corresponding":false},{"id":850313,"name":"Dawei Bu","orcid":null,"position":3,"is_corresponding":false},{"id":705434,"name":"Joseph M. Rutkowski","orcid":"0000-0002-4197-0236","position":4,"is_corresponding":false},{"id":1070365,"name":"Joel P. Berger","orcid":null,"position":5,"is_corresponding":false},{"id":283831,"name":"Christine M. Kusminski","orcid":null,"position":6,"is_corresponding":false},{"id":284582,"name":"Ningyan Zhang","orcid":"0000-0002-4348-2180","position":7,"is_corresponding":false},{"id":105313,"name":"Zhiqiang An","orcid":"0000-0001-9309-2335","position":8,"is_corresponding":false},{"id":275031,"name":"Philipp E. Scherer","orcid":"0000-0003-0680-3392","position":9,"is_corresponding":false},{"id":282942,"name":"Yu An","orcid":"0000-0002-9678-3382","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:31.133446Z","pmid":"36696925","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":[]}