HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury

Ning Li; Bohao Liu; Ruyuan He; Guorui Li; Rui Xiong; Tinglv Fu; Donghang Li; Chenzhen Xu; Bo Wang; Qing Geng

doi:10.1016/j.isci.2023.107158

HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury

iScience. 2023 Jun 19;26(7):107158. doi: 10.1016/j.isci.2023.107158. eCollection 2023 Jul 21.

Authors

Ning Li¹, Bohao Liu^{1

2}, Ruyuan He¹, Guorui Li¹, Rui Xiong¹, Tinglv Fu¹, Donghang Li¹, Chenzhen Xu¹, Bo Wang¹, Qing Geng¹

Affiliations

¹ Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
² Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130021, China.

Abstract

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.

Keywords: Biochemistry; Molecular biology.