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Trans-NIH Angiogenesis Workshop; May 20-21, 2013
  • Abstracts

    miRNA in Diabetic Wound Healing

    Sashwati Roy, PhD  [ View bio ]
    (Yale University, New Haven, Connecticut)

    Impairment of dermal wound healing is a debilitating complication commonly encountered during diabetes mellitus. Dysregulated inflammatory and angiogenesis phases are key players in the impairment of diabetic wound healing. Emerging studies indicate that miRNAs play a key role in regulating several hubs that orchestrate the wound inflammation and angiogenesis processes. Our laboratory first reported dysfunction in wound macrophage efferocytosis function leading to impaired resolution of wound inflammation in diabetic wounds. Recent studies from our laboratory indicate a key role of miR-21 in resolution of wound inflammation. The expression of miR-21 is decreased in the macrophages from diabetic wounds. Oxidants generated during inflammation may play a central role in supporting tissue vascularization. Immune cells from diabetics show attenuated NADPH oxidase response. We provided first evidence demonstrating that miRNAs regulate cellular redox environment via a NADPH oxidase- dependent mechanism in human microvascular endothelial cells (HMECs). We further demonstrated that hypoxia-sensitive miR-200b is involved in induction of angiogenesis by directly targeting Ets-1 GATA2 and VEGFR2 in HMECs. Downregulation of miR-200b derepressed GATA2 and VEGFR2 expression to switch on wound angiogenesis that was disrupted in diabetic wounds. Treatment of endothelial cells with tumor necrosis factor (TNF)-a, a proinflammatory cytokine abundant in diabetic wounds, induced miR-200b expression, silenced GATA2 and VEGFR2, and suppressed angiogenesis. These outcomes were attenuated using anti-miR-200b strategy. Neutralization of TNF-a in the diabetic wounds improved wound angiogenesis and closure, which was accompanied by downregulation of miR-200b expression and desilencing of GATA2 and VEGFR2. These studies point toward a key role of miRNA in diabetic wound healing. Supported by RO1 DK 076566 to SR.

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Workshop Organizer: NIH

NCI:Nancy Emenaker, PhD, RD
Suzanne Forry-Schaudies, PhD
NHLBI:Yunling Gao, MD, PhD
NIDDK: Teresa Jones, MD

NIH - National Institutes of Health: Turning Discovery Into Health


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