Journal article
Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing
Frontiers in immunology, Vol.8, pp.635-635
06/01/2017
DOI: 10.3389/fimmu.2017.00635
PMCID: PMC5451506
PMID: 28620387
Abstract
Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (
DNMAML
floxed
Lyz2
Cre+
) demonstrated delayed early healing (days 1–3) and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D), Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in
Notch1
and
Notch2
was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (
DNMAML
floxed
Lyz2
Cre+
on a high-fat diet), improved wound healing was seen at late time points (days 6–7). These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.
Details
- Title: Subtitle
- Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing
- Creators
- Andrew S. Kimball - University of MichiganAmrita D. Joshi - University of MichiganAnna E. Boniakowski - University of MichiganMatthew Schaller - University of MichiganJooho Chung - University of MichiganRonald Allen - University of MichiganJennifer Bermick - University of MichiganWilliam F. Carson - University of MichiganPeter K. Henke - University of MichiganIvan Maillard - University of MichiganSteve L. Kunkel - University of MichiganKatherine A. Gallagher - University of Michigan
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.8, pp.635-635
- DOI
- 10.3389/fimmu.2017.00635
- PMID
- 28620387
- PMCID
- PMC5451506
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Publisher
- Frontiers Media S.A
- Grant note
- DK-102357 / National Institutes of Health
- Language
- English
- Date published
- 06/01/2017
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984354009802771
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