WCN26-3666 Semaglutide Combined with Physical Training: Impact on Diabetic Kidney Disease Morbidity

Results: Administration of finerenone significantly reduced albuminuria in eNOS-KO db/db mice compared to the eNOS-KO db/db vehicletreated group.Increased infiltration of macrophages, as detected by F4/ 80 immunostaining, was observed in the kidneys of eNOS-KO db/db mice relative to control mice.Finerenone treatment markedly attenuated this macrophage infiltration.In BMDMs cultured in aldosteronecontaining media, finerenone suppressed LPS-induced secretion of IL-6 to supernatant.Aldosterone stimulation led to an upregulation of TRPC5 protein expression in BMDMs.Notably, inhibition of TRPC5, but not TRPC6, completely abolished LPS-induced IL-6 expression and secretion.Furthermore, LPS stimulation triggered a calcium (Ca 2+ ) influx in BMDMs, which was effectively suppressed by TRPC5 inhibition.These findings suggest that the aldosterone-MR-TRPC5 signaling pathway contributes to inflammatory responses in macrophages, potentially via the NF-B pathway.Conclusion: Our study suggests that the renal protective effects of finerenone are at least partly mediated by suppression of chronic inflammation.We revealed that the MR-TRPC5 pathway in macrophage has a pivotal role of maitainof chronic inflammation in kidney diseases.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.