| First Author | Li N | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 7 | Pages | 107158 |
| PubMed ID | 37404376 | Mgi Jnum | J:352489 |
| Mgi Id | MGI:7508797 | Doi | 10.1016/j.isci.2023.107158 |
| Citation | Li N, et al. (2023) HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury. iScience 26(7):107158 |
| abstractText | Activated inflammation and pyroptosis in macrophage are closely associated with acute lung injury (ALI). Histone deacetylase 3 (HDAC3) serves as an important enzyme that could repress gene expression by mediating chromatin remodeling. In this study, we found that HDAC3 was highly expressed in lung tissues of lipopolysaccharide (LPS)-treated mice. Lung tissues from macrophage HDAC3-deficient mice stimulated with LPS showed alleviative lung pathological injury and inflammatory response. HDAC3 silencing significantly blocked the activation of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway in LPS-induced macrophage. LPS could recruit HDAC3 and H3K9Ac to the miR-4767 gene promoter, which repressed the expression of miR-4767 to promote the expression of cGAS. Taken together, our findings demonstrated that HDAC3 played a pivotal role in mediating pyroptosis in macrophage and ALI by activating cGAS/STING pathway through its histone deacetylation function. Targeting HDAC3 in macrophage may provide a new therapeutic target for the prevention of LPS-induced ALI. |
