Proliferation of renal macrophage via MR/CSF1 pathway induced with aldosterone and inhibited by esaxerenone.

Macrophage proliferation plays a critical role in kidney injury and repair, but due to their high plasticity and heterogeneity, the origins and subtypes of these proliferating cells remain unclear. This study investigates aldosterone-induced proliferation of renal macrophages, focusing on their origins, subtypes, and regulatory mechanisms using immunofluorescence, flow cytometry, and single-cell sequencing. The findings suggest that both resident and infiltrating macrophages proliferate in response to aldosterone, a significant proportion of which are renal resident macrophages, predominantly of the M1 subtype. The study also identifies the mineralocorticoid receptor/colony stimulation factor-1 (MR/CSF1) pathway as a key regulator of this process. Inhibition of this pathway through antagonists and inhibitors reduces macrophage proliferation and kidney damage, suggesting that targeting MR/CSF1 could be therapeutic against aldosterone-induced renal damage and inflammation.