ArticleFrontiers in physiology2026
Podocyte-specific acid sphingomyelinase overexpression promotes gasdermin D dependent pyroptosis by impairing autophagic flux during obesity.
Article in Frontiers in physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Recent studies suggest that gasdermin D (GSDMD) pore formation contributes to inflammasome-mediated cytokine release and pyroptosis in podocytes under pathological conditions. However, the molecular mechanisms regulating GSDMD pore formation in these cells remain unclear. Given the established role of the lysosomal acid sphingomyelinase (ASM)-ceramide pathway in obesity-related glomerulopathy (ORG), we investigated whether ASM regulates obesity-induced GSDMD pore formation and pyroptosis in podocytes, thereby influencing the progression of ORG. We found that podocyte-specific Smpd1 (the gene encoding ASM) overexpression markedly enhanced high-fat diet (HFD)-induced NLRP3 inflammasome activation, GSDMD N-terminal fragment (GSDMD-NT) generation, and pyroptosis in glomeruli of Smpd1
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