β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4
Summary: Fibrosis, characterized by sustained activation of myofibroblasts and excessive extracellular matrix (ECM) deposition, is known to be associated with chronic inflammation. Receptor-interacting protein kinase 3 (RIPK3), the central kinase of necroptosis signaling, is upregulated in fibrosis...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723013347 |
| _version_ | 1827630378107535360 |
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| author | Zhiqi Sun Filippo M. Cernilogar Helena Horvatic Assa Yeroslaviz Zeinab Abdullah Gunnar Schotta Veit Hornung |
| author_facet | Zhiqi Sun Filippo M. Cernilogar Helena Horvatic Assa Yeroslaviz Zeinab Abdullah Gunnar Schotta Veit Hornung |
| author_sort | Zhiqi Sun |
| collection | DOAJ |
| description | Summary: Fibrosis, characterized by sustained activation of myofibroblasts and excessive extracellular matrix (ECM) deposition, is known to be associated with chronic inflammation. Receptor-interacting protein kinase 3 (RIPK3), the central kinase of necroptosis signaling, is upregulated in fibrosis and contributes to tumor necrosis factor (TNF)-mediated inflammation. In bile-duct-ligation-induced liver fibrosis, we found that myofibroblasts are the major cell type expressing RIPK3. Genetic ablation of β1 integrin, the major profibrotic ECM receptor in fibroblasts, not only abolished ECM fibrillogenesis but also blunted RIPK3 expression via a mechanism mediated by the chromatin-remodeling factor chromodomain helicase DNA-binding protein 4 (CHD4). While the function of CHD4 has been conventionally linked to the nucleosome-remodeling deacetylase (NuRD) and CHD4-ADNP-HP1(ChAHP) complexes, we found that CHD4 potently repressed a set of genes, including Ripk3, with high locus specificity but independent of either the NuRD or the ChAHP complex. Thus, our data uncover that β1 integrin intrinsically links fibrotic signaling to RIPK3-driven inflammation via a novel mode of action of CHD4. |
| first_indexed | 2024-03-09T14:06:00Z |
| format | Article |
| id | doaj.art-8a12caf9c5604b6ab7e0d6ecc9a72dba |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:06:00Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8a12caf9c5604b6ab7e0d6ecc9a72dba2023-11-30T05:06:46ZengElsevierCell Reports2211-12472023-11-014211113322β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4Zhiqi Sun0Filippo M. Cernilogar1Helena Horvatic2Assa Yeroslaviz3Zeinab Abdullah4Gunnar Schotta5Veit Hornung6Gene Center and Department of Biochemistry, Ludwig Maximilian University of Munich, Munich, Germany; Research Group Molecular Mechanisms of Inflammation, Max-Planck Institute of Biochemistry, Martinsried, Germany; Corresponding authorDivision of Molecular Biology, Biomedical Center, Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, GermanyInstitute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, GermanyComputational Biology Group, Max-Planck Institute of Biochemistry, Martinsried, GermanyInstitute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, GermanyDivision of Molecular Biology, Biomedical Center, Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, GermanyGene Center and Department of Biochemistry, Ludwig Maximilian University of Munich, Munich, Germany; Research Group Molecular Mechanisms of Inflammation, Max-Planck Institute of Biochemistry, Martinsried, Germany; Corresponding authorSummary: Fibrosis, characterized by sustained activation of myofibroblasts and excessive extracellular matrix (ECM) deposition, is known to be associated with chronic inflammation. Receptor-interacting protein kinase 3 (RIPK3), the central kinase of necroptosis signaling, is upregulated in fibrosis and contributes to tumor necrosis factor (TNF)-mediated inflammation. In bile-duct-ligation-induced liver fibrosis, we found that myofibroblasts are the major cell type expressing RIPK3. Genetic ablation of β1 integrin, the major profibrotic ECM receptor in fibroblasts, not only abolished ECM fibrillogenesis but also blunted RIPK3 expression via a mechanism mediated by the chromatin-remodeling factor chromodomain helicase DNA-binding protein 4 (CHD4). While the function of CHD4 has been conventionally linked to the nucleosome-remodeling deacetylase (NuRD) and CHD4-ADNP-HP1(ChAHP) complexes, we found that CHD4 potently repressed a set of genes, including Ripk3, with high locus specificity but independent of either the NuRD or the ChAHP complex. Thus, our data uncover that β1 integrin intrinsically links fibrotic signaling to RIPK3-driven inflammation via a novel mode of action of CHD4.http://www.sciencedirect.com/science/article/pii/S2211124723013347CP: Immunology |
| spellingShingle | Zhiqi Sun Filippo M. Cernilogar Helena Horvatic Assa Yeroslaviz Zeinab Abdullah Gunnar Schotta Veit Hornung β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4 Cell Reports CP: Immunology |
| title | β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4 |
| title_full | β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4 |
| title_fullStr | β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4 |
| title_full_unstemmed | β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4 |
| title_short | β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4 |
| title_sort | β1 integrin signaling governs necroptosis via the chromatin remodeling factor chd4 |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723013347 |
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