Hematopoietic-specific melanocortin 1 receptor signaling protects against nephrotoxic serum nephritis and mediates the beneficial effect of melanocortin therapy.

ABSTRACT: The melanocortin hormone system has emerged as a novel therapeutic target for treating refractory glomerular diseases. However, the role of hematopoietic melanocortin 1 receptor (MC1R) signaling remains unknown. Upon insult by rabbit nephrotoxic serum, MC1R null-mutant mice developed more severe crescentic glomerulonephritis than wild-type mice, marked by aggravated proteinuria, kidney dysfunction and histologic lesions. Melanocortin therapy, using Repository Corticotropin Injection (Acthar Gel), the pan-melanocortin receptor agonist NDP-MSH, or the MC1R agonist MS05, ameliorated experimental nephritis in wild-type mice but this effect was blunted in null mice. Exacerbated experimental nephritis in null mice was associated with increased glomerular deposition of autologous IgG and C5b-9, i

SUBMITTER: Guan X 

PROVIDER: S-EPMC10431720 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature