Intercepting the complement amplification loop through podocyte MC5R signaling ameliorates membranous nephropathy.

ABSTRACT: Melanocortin therapy has demonstrated potential in improving membranous nephropathy in human patients. The underlying mechanisms remain unclear. Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the nonsteroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated proteinuria, and ameliorated glomerulopathy. In contrast, MC5R knockout exacerbated membranous nephropathy, while abolishing the beneficial effects of melanocortins. Mechanistically, MC5R expression was evident in podocytes in wild-type mice, and podocyte MC5R appears to protect against membranous nephropathy, as demonstrated by its necessity for melanocort

SUBMITTER: Liu J 

PROVIDER: S-EPMC12636283 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature