title: The role of microRNA-15b in the impaired angiogenesis in diabetic wounds.
abstract: The impairment in diabetic wound healing represents a significant clinical problem. Decreased angiogenesis is thought to play a central role in the pathogenesis of this impairment. We have previously shown that treatment of diabetic murine wounds with mesenchymal stem cells can improve healing, but the mechanisms are not completely defined. MicroRNA-15b (miR-15b) has been implicated in the regulation of the angiogenic response. We hypothesized that abnormal miR-15b expression may contribute to the impaired angiogenesis observed in impaired diabetic wound healing. To test this hypothesis, we examined the expression of miR-15b and its target genes in diabetic and nondiabetic mice before and after injury. MiR-15b expression was significantly up-regulated in diabetic mouse wounds during the wound healing response. Increased miR-15b levels also closely correlated with decreased gene expression of its proangiogenic target genes. Furthermore, the correction of the diabetic wound healing impairment with mesenchymal stem cell treatment was associated with a significant decrease in miR-15b expression level and increased gene expression of its proangiogenic target genes. These results provide the first evidence that increased expression of miR-15b in diabetic wounds in response to injury may, in part, be responsible for the abnormal angiogenic response seen in diabetic wounds and may contribute to the observed wound healing impairment.
authors: Sanford Burnham Medical Research Institute, Nemours Children's Hospital, Orlando, Florida; Department of Surgery, Children's Hospital Colorado, School of Medicine, University of Colorado, Aurora, Colorado.
authors: Junwang
authors: J
authors: Xu
authors: Carlos
authors: C
authors: Zgheib
authors: Junyi
authors: J
authors: Hu
authors: Wenjie
authors: W
authors: Wu
authors: Liping
authors: L
authors: Zhang
authors: Kenneth W
authors: KW
authors: Liechty
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus; D004195:Disease Models, Animal; D015870:Gene Expression; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics*; D014947:Wounds and Injuries / Q000150:complications / Q000235:genetics* / Q000378:metabolism
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; C570833:Mirn15 microRNA, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C052617:Bcl2 protein, mouse