HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury
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...
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| Language: | English |
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Elsevier
2023-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422301235X |
| _version_ | 1827895486504239104 |
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| author | Ning Li Bohao Liu Ruyuan He Guorui Li Rui Xiong Tinglv Fu Donghang Li Chenzhen Xu Bo Wang Qing Geng |
| author_facet | Ning Li Bohao Liu Ruyuan He Guorui Li Rui Xiong Tinglv Fu Donghang Li Chenzhen Xu Bo Wang Qing Geng |
| author_sort | Ning Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T22:21:40Z |
| format | Article |
| id | doaj.art-4e0b58d870904b33a2c6c9416b1e59fa |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:21:40Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4e0b58d870904b33a2c6c9416b1e59fa2023-07-23T04:55:45ZengElsevieriScience2589-00422023-07-01267107158HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injuryNing Li0Bohao Liu1Ruyuan He2Guorui Li3Rui Xiong4Tinglv Fu5Donghang Li6Chenzhen Xu7Bo Wang8Qing Geng9Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China; Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130021, ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China; Corresponding authorDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S258900422301235XBiochemistryMolecular biology |
| spellingShingle | Ning Li Bohao Liu Ruyuan He Guorui Li Rui Xiong Tinglv Fu Donghang Li Chenzhen Xu Bo Wang Qing Geng HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury iScience Biochemistry Molecular biology |
| title | HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury |
| title_full | HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury |
| title_fullStr | HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury |
| title_full_unstemmed | HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury |
| title_short | HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury |
| title_sort | hdac3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury |
| topic | Biochemistry Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422301235X |
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