Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a

Basak Icli, Christoph S. Nabzdyk, Jorge Lujan-Hernandez, Meghan Cahill, Michael E. Auster, A. K.M. Wara, Xinghui Sun, Denizhan Ozdemir, Giorgio Giatsidis, Dennis P. Orgill, Mark W. Feinberg

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Wound healing is a physiological reparative response to injury and a well-orchestrated process that involves hemostasis, cellular migration, proliferation, angiogenesis, extracellular matrix deposition, and wound contraction and re-epithelialization. However, patients with type 2 diabetes mellitus (T2D) are frequently afflicted with impaired wound healing that progresses into chronic wounds or diabetic ulcers, and may lead to complications including limb amputation. Herein, we investigate the potential role of microRNA-26a (miR-26a) in a diabetic model of wound healing. Expression of miR-26a is rapidly induced in response to high glucose in endothelial cells (ECs). Punch skin biopsy wounding of db/db mice revealed increased expression of miR-26a (~. 3.5-fold) four days post-wounding compared to that of WT mice. Local administration of a miR-26a inhibitor, LNA-anti-miR-26a, induced angiogenesis (up to ~. 80%), increased granulation tissue thickness (by 2.5-fold) and accelerated wound closure (53% after nine days) compared to scrambled anti-miR controls in db/db mice. These effects were independent of altered M1/M2 macrophage ratios. Mechanistically, inhibition of miR-26a increased its target gene SMAD1 in ECs nine days post-wounding of diabetic mice. In addition, high glucose reduced activity of the SMAD1-3'-UTR. Diabetic dermal wounds treated with LNA-anti-miR-26a had increased expression of ID1, a downstream modulator or SMAD1, and decreased expression of the cell cycle inhibitor p27. These findings establish miR-26a as an important regulator on the progression of skin wounds of diabetic mice by specifically regulating the angiogenic response after injury, and demonstrate that neutralization of miR-26a may serve as a novel approach for therapy.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
StatePublished - Feb 1 2016
Externally publishedYes


  • Angiogenesis
  • Diabetes
  • MicroRNA
  • Wound healing

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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