SIRT3 Regulates Macrophage-Mediated Inflammation in Diabetic Wound Repair
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved..
Control of inflammation is critical for the treatment of nonhealing wounds, but a delicate balance exists between early inflammation that is essential for normal tissue repair and the pathologic inflammation that can occur later in the repair process. This necessitates the development of novel therapies that can target inflammation at the appropriate time during repair. Here, we found that SIRT3 is essential for normal healing and regulates inflammation in wound macrophages after injury. Under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in dysregulated inflammation. In addition, we found that FABP4 regulates SIRT3 in human blood monocytes, and inhibition of FABP4 in wound macrophages decreases inflammatory cytokine expression, making FABP4 a viable target for the regulation of excess inflammation and wound repair in diabetes. Using a series of ex vivo and in vivo studies with genetically engineered mouse models and diabetic human monocytes, we showed that FABP4 expression is epigenetically upregulated in diabetic wound macrophages and, in turn, diminishes SIRT3 expression, thereby promoting inflammation. These findings have significant implications for controlling inflammation and promoting tissue repair in diabetic wounds.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:139 |
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| Enthalten in: |
The Journal of investigative dermatology - 139(2019), 12 vom: 25. Dez., Seite 2528-2537.e2 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Boniakowski, Anna M [VerfasserIn] |
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| Links: |
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| Themen: |
EC 3.5.1.- |
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| Anmerkungen: |
Date Completed 05.06.2020 Date Revised 10.04.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jid.2019.05.017 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Control of inflammation is critical for the treatment of nonhealing wounds, but a delicate balance exists between early inflammation that is essential for normal tissue repair and the pathologic inflammation that can occur later in the repair process. This necessitates the development of novel therapies that can target inflammation at the appropriate time during repair. Here, we found that SIRT3 is essential for normal healing and regulates inflammation in wound macrophages after injury. Under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in dysregulated inflammation. In addition, we found that FABP4 regulates SIRT3 in human blood monocytes, and inhibition of FABP4 in wound macrophages decreases inflammatory cytokine expression, making FABP4 a viable target for the regulation of excess inflammation and wound repair in diabetes. Using a series of ex vivo and in vivo studies with genetically engineered mouse models and diabetic human monocytes, we showed that FABP4 expression is epigenetically upregulated in diabetic wound macrophages and, in turn, diminishes SIRT3 expression, thereby promoting inflammation. These findings have significant implications for controlling inflammation and promoting tissue repair in diabetic wounds | ||
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| 700 | 1 | |a Joshi, Amrita |e verfasserin |4 aut | |
| 700 | 1 | |a Kimball, Andrew S |e verfasserin |4 aut | |
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| 700 | 1 | |a Gudjonsson, Johann E |e verfasserin |4 aut | |
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| 700 | 1 | |a Kunkel, Steve L |e verfasserin |4 aut | |
| 700 | 1 | |a Gallagher, Katherine A |e verfasserin |4 aut | |
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