Macrophage BACH1, a heme regulated transcriptional repressor, controls HMOX1 and skeletal muscle regeneration
Skeletal muscle regeneration following injury is a complex process that involves inflammatory components. Macrophage infiltration to damaged tissues upon injuries and their in‐situ differentiation into effector/inflammatory and repair macrophages is indispensable for necrotic debris clearance, and for coordination of tissue repair. Regulatory events controlling the highly dynamic macrophage phenotype switch are not well understood. Here, by using an acute sterile skeletal muscle injury model, and by studying macrophage chromatin accessibility (ATAC‐seq) and gene expression (RNA‐seq) dynamics during inflammation and tissue regeneration, we identified a heme‐ and MARE motif binding transcription factor, BTB Domain And CNC Homolog 1 (BACH1), as a novel regulatory molecule of the macrophage phenotype switch following tissue injury. We show that Bach1 deletion impairs muscle regeneration, alters the dynamics of the macrophage phenotype transition, impacts myoblast proliferation and leads to transcriptional deregulation of critical inflammatory and repair‐related genes. We also find that BACH1 directly binds and regulates distal regulatory elements of these genes, suggesting a role of BACH1 in controlling a spectrum of the inflammatory and tissue repair response genes in macrophages upon tissue injury. As proof of concept, inactivation of heme oxygenase 1 (Hmox1), a known downstream BACH1 target and the most deregulated gene in the Bach1 KO, in macrophages, impairs muscle regeneration by changing the dynamics of the macrophage phenotype switch. Collectively, our data suggest the existence of a regulatory axis, involving BACH1 and HMOX1 that control the phenotype and function of the infiltrating myeloid cells upon tissue damage, shaping the overall tissue repair kinetics. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
The FASEB Journal - 33(2019), S1, Seite 868.20-868.20 |
| Beteiligte Personen: |
Patsalos, Andreas [VerfasserIn] |
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| BKL: |
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| Anmerkungen: |
© Federation of American Societies for Experimental Biology |
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| Umfang: |
1 |
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| doi: |
10.1096/fasebj.2019.33.1_supplement.868.20 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Macrophage BACH1, a heme regulated transcriptional repressor, controls HMOX1 and skeletal muscle regeneration |
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| 520 | |a Skeletal muscle regeneration following injury is a complex process that involves inflammatory components. Macrophage infiltration to damaged tissues upon injuries and their in‐situ differentiation into effector/inflammatory and repair macrophages is indispensable for necrotic debris clearance, and for coordination of tissue repair. Regulatory events controlling the highly dynamic macrophage phenotype switch are not well understood. Here, by using an acute sterile skeletal muscle injury model, and by studying macrophage chromatin accessibility (ATAC‐seq) and gene expression (RNA‐seq) dynamics during inflammation and tissue regeneration, we identified a heme‐ and MARE motif binding transcription factor, BTB Domain And CNC Homolog 1 (BACH1), as a novel regulatory molecule of the macrophage phenotype switch following tissue injury. We show that Bach1 deletion impairs muscle regeneration, alters the dynamics of the macrophage phenotype transition, impacts myoblast proliferation and leads to transcriptional deregulation of critical inflammatory and repair‐related genes. We also find that BACH1 directly binds and regulates distal regulatory elements of these genes, suggesting a role of BACH1 in controlling a spectrum of the inflammatory and tissue repair response genes in macrophages upon tissue injury. As proof of concept, inactivation of heme oxygenase 1 (Hmox1), a known downstream BACH1 target and the most deregulated gene in the Bach1 KO, in macrophages, impairs muscle regeneration by changing the dynamics of the macrophage phenotype switch. Collectively, our data suggest the existence of a regulatory axis, involving BACH1 and HMOX1 that control the phenotype and function of the infiltrating myeloid cells upon tissue damage, shaping the overall tissue repair kinetics. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal. | ||
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