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Podocyte-specific silencing of acid sphingomyelinase gene to abrogate hyperhomocysteinemia-induced NLRP3 inflammasome activation and glomerular inflammation

Year: 2024
Type: article
Abstract: In the present study, we tested whether podocyte-specific silencing of Smpd1 gene attenuates hyperhomocysteinemia (hHcy)-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and associated inflammatory extracellular vesicle (EV) release in podocytes and thereby suppresses glomerular inflammatory response and injury. Our findings suggest that acid sphingomyelinase (ASM) in podocytes plays a crucial role in the control of NLRP3 inflammasome activation and inflammatory EV release during hHcy. Based on our findings, it is anticipated that the development of podocyte-specific ASM inhibition or Smpd1 gene silencing may be a novel therapeutic strategy for treatment of hHcy-induced glomerular disease with minimized side effects.
DOI: 10.1152/ajprenal.00195.2023
Authors: Dandan Huang, Jason M. Kidd, Yao Zou, Xiaoyuan Wu, Ningjun Li, Todd W. B. Gehr, Pin-Lan Li, Guangbi Li
Language: English
Open Access status: green
Awards: G2938117937, G3603235994, Hypertension and glomerular injury in hyperhomocysteinemia - role of inflammatory exosomes, Lysosome dysfunction in podocytopathy and associated hypertension, G9000037534, G9000149670
OpenAlex ID: W4394920779
FWCI: 0.923
Cites: 65
Cited by: 8
Related to: 10