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
Affiliations
Ning Li
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Bohao Liu
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China; Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130021, China
Ruyuan He
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Guorui Li
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Rui Xiong
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Tinglv Fu
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Donghang Li
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Chenzhen Xu
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Bo Wang
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China; Corresponding author
Qing Geng
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China; Corresponding author
Summary: 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.
