ArticleKidney international2025
Melanocortin 5 receptor signaling protects against podocyte injury in proteinuric glomerulopathies.
Article in Kidney international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
5 citing papers in PubMed.
- The Synthetic Melanocortin Agonist NDP-MSH Ameliorates THSD7A-Associated Membranous Nephropathy in an Active Immunization Mouse Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- B7-1 and PD-L1 crosstalk in podocyte injury: from molecular mechanisms to novel therapeutic strategies for nephrotic syndrome.International urology and nephrology · 2026Review
- Application of the nephrotoxic serum nephritis model in glomerulonephritis research.Molecular medicine (Cambridge, Mass.) · 2026Review
- Intercepting the complement amplification loop through podocyte MC5R signaling ameliorates membranous nephropathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Melanocortins: A new paradigm in immunotherapy for membranous nephropathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Melanocortin therapeutics, exemplified by adrenocorticotropic hormone, have a proven steroidogenic-independent anti-proteinuric and glomerular protective effect. The biological functions of melanocortins are mediated by melanocortin receptors (MCR), including MC1R, which recent studies have shown to protect against glomerular disease. However, the role of other MCRs like MC5R is unknown. Here, Mc5r knockout exacerbated glomerulopathy in mice injured by adriamycin (ADR) or nephrotoxic serum (NTS), as demonstrated by increased albuminuria and podocyte injury. Conversely, selective MC5R agonism using a peptidomimetic agonist improved outcomes of glomerulopathies. Mechanistically, MC5R is expressed in glomerular podocytes. Reconstitution of MC5R in podocytes attenuated glomerular injury and proteinuria in Mc5r knockout mouse models of glomerulopathies, indicating a direct podocyte protective effect. In vitro, MC5R agonism in primary wild-type podocytes attenuated ADR-elicited cytoskeleton disruption, hypermotility and apoptosis, associated with restored inhibitory phosphorylation of glycogen synthases kinase 3β (GSK3β), a signaling transducer downstream of MC5R and at the nexus of multiple podocytopathic pathways. In parallel, ADR-induced phosphorylation and activation of GSK3β substrates, such as paxillin and NF-κB Rela/p65, were abrogated, leading to improved actin cytoskeleton integrity and diminished expression of mediators of podocyte injury, like MCP-1, B7-1 and Cathepsin L. This protective effect of MC5R agonism was blunted in wild-type podocytes expressing constitutively active GSK3β and was mimicked in Mc5r knockout podocytes by ectopic expression of dominant negative GSK3β. Consistently in ADR-injured Mc5r knockout mice, worsened podocytopathy was associated with enhanced GSK3β hyperactivity. These findings suggest that MC5R signaling protects against podocyte injury and may serve as a novel therapeutic target for glomerular diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.