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Faculty, Staff and Student Publications
Publication Date
3-1-2023
Journal
Molecular Metabolism
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.
Keywords
Mice, Animals, Podocytes, Peptide Fragments, Fibrosis, Renal Insufficiency, Chronic, Antibodies
DOI
10.1016/j.molmet.2023.101680
PMID
36696925
PMCID
PMC9918787
PubMedCentral® Posted Date
January 2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Bioinformatics Commons, Biomedical Informatics Commons, Medical Molecular Biology Commons
Comments
Supplementary Material
PMID: 36696925