Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.

ABSTRACT: While significant advances have been made in understanding renal pathophysiology, less is known about the role of glycosphingolipid (GSL) metabolism in driving organ dysfunction. Here, we used a small molecule inhibitor of glucosylceramide synthase to modulate GSL levels in three mouse models of distinct renal pathologies: Alport syndrome (Col4a3 KO), polycystic kidney disease (Nek8^jck), and steroid-resistant nephrotic syndrome (Nphs2 cKO). At the tissue level, we identified a core immune-enriched transcriptional signature that was shared across models and enriched in human polycystic kidney disease. Single nuclei analysis identified robust transcriptional changes across multiple kidney cell types, including epithelial and immune lineages. To further explore the role of GSL modu

SUBMITTER: Cheong A 

PROVIDER: S-EPMC11297156 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature