2026-10-12T13:07:16Z https://www.scidb.cn/oai

10.57760/sciencedb.07985 2023-04-21T16:11:28Z

2023-04-21 GDF15 regulated by HDAC2 exerts suppressive effects on oxygen and glucose deprivation-induced pyroptosis via NLRP3/Caspase-1/ GSDMD pathway doi:10.57760/sciencedb.07985 en Purpose: Pyroptosis, inflammation-related programed cell death mediated by NLRP3 inflammasome, plays a critical role in the pathogenesis of cerebral hypoxic-ischemic injury. Our study aims to explore the biological role of growth differentiation factor (GDF)15 in oxygen-glucose deprivation (OGD)-induced pyroptosis. Methods: HT22 neurons were subjected to OGD to simulate cerebral hypoxic-ischemic injury. HT22 neurons were transfected with plasmids to overexpress GDF15, or shRNAs constructs to silence GDF15. ELISA assay was used to detect GDF15, interleukin-1β (IL-1β), IL-18, and neuron specific enolase (NSE) in culture medium. Cells pyroptosis was measured by flow cytometery. Chromatin immuno-precipitation assay was used to detect interaction of H3K27ac with GDF15 promoter. Results: OGD exposure caused significant increases in medium levels of IL-1, IL-18 and NSE, percentages of pyroptotic cells, and NLRP3, caspase-1, and gasdermin D (GSDMD) protein, which were markedly reversed by GDF15 overexpression (p-value < 0.001). GDF15 knockdown resulted in significant increases in medium levels of IL-1, IL-18 and NSE, percentages of pyroptotic cells, and caspase-1 and GSDMD protein (p-value < 0.001). The GDF15 knockdown-induced effects were counteracted by treatment with NLRP3 inhibitor. OGD decreased H3K27ac enrichment with promoter of GDF15 to down-regulate GDF15, but was compromised by co-treatment with HDAC2 inhibitor. Conclusion: Our data demonstrates that GDF15 attenuates OGD/R-induced pyroptosis through NLRP3/Caspase-1/GSDMD pathway. HDAC2 is involves in mediating OGD-induced GDF15 down-regulation via H3K27ac enrichment. GDF15 overexpression and HDAC2 inhibition hold potential as useful therapeutic strategies for neuroprotection. GDF15; oxygen-glucose deprivation; cerebral hypoxic-ischemic injury Xiao Hua Shengtao Yao Yan Li PUBLIC https://creativecommons.org/publicdomain/zero/1.0/ dataset Science Data Bank