Journal article
SIRT3 Regulates Macrophage-Mediated Inflammation in Diabetic Wound Repair
Journal of investigative dermatology, Vol.139(12), pp.2528-2537.e2
12/01/2019
DOI: 10.1016/j.jid.2019.05.017
PMCID: PMC7185380
PMID: 31207226
Abstract
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.
Details
- Title: Subtitle
- SIRT3 Regulates Macrophage-Mediated Inflammation in Diabetic Wound Repair
- Creators
- Anna M. Boniakowski - University of MichiganAaron D. denDekker - University of MichiganFrank M. Davis - University of MichiganAmrita Joshi - University of MichiganAndrew S. Kimball - University of MichiganMatthew Schaller - University of MichiganRon Allen - Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USAJennifer Bermick - University of MichiganDylan Nycz - University of MichiganMary E. Skinner - University of MichiganScott Robinson - University of MichiganAndrea T. Obi - University of MichiganBethany B. Moore - University of MichiganJohann E. Gudjonsson - University of MichiganDavid Lombard - University of MichiganSteve L. Kunkel - University of MichiganKatherine A. Gallagher - University of Michigan
- Resource Type
- Journal article
- Publication Details
- Journal of investigative dermatology, Vol.139(12), pp.2528-2537.e2
- DOI
- 10.1016/j.jid.2019.05.017
- PMID
- 31207226
- PMCID
- PMC7185380
- NLM abbreviation
- J Invest Dermatol
- ISSN
- 0022-202X
- eISSN
- 1523-1747
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- R35HL144481 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 HL137919; 00060733 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 12/01/2019
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984354054702771
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