title: Anti-microRNA-378a enhances wound healing process by upregulating integrin beta-3 and vimentin.
abstract: Delayed or impaired wound healing is a major public health issue worldwide, especially in patients with diabetes mellitus and vascular atherosclerosis. MicroRNAs have been identified as key regulators of wound healing. Here, we show that miR-Pirate378a transgenic mice (and thus have inhibited miR-378a-5p function) display enhanced wound healing. Expression of vimentin and β3 integrin, two important modulators of wound healing, is markedly elevated in the transgenic mice. MiR-Pirate378a-transfected cells display greater mobility during migration assays, which was hypothesized to be due to the upregulation of vimentin and β3 integrin. Both molecules were confirmed to be targets of miR-378a, and thus their expression could be rescued by miR-Pirate378a. Overexpression of vimentin also contributed to fibroblast differentiation, and upregulation of β3 integrin was responsible for increased angiogenesis. Mice treatment with miR-Pirate378a-conjugated nanoparticles displayed enhanced wound healing. Thus, we have demonstrated that knockdown of miR-378a increased the expression of its target proteins, vimentin, and β3 integrin, which accelerated fibroblast migration and differentiation in vitro and enhanced wound healing in vivo.
authors: 1] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Haoran
authors: H
authors: Li
authors: 1] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Leslie
authors: L
authors: Chang
authors: 1] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: William W
authors: WW
authors: Du
authors: 1] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Shaan
authors: S
authors: Gupta
authors: 1] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Azam
authors: A
authors: Khorshidi
authors: 1] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Michael
authors: M
authors: Sefton
authors: 1] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors: Burton B
authors: BB
authors: Yang
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D039661:Integrin beta3 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics; D020320:Oligoribonucleotides, Antisense / Q000235:genetics*; D034622:RNA Interference; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D039661:Integrin beta3; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D020320:Oligoribonucleotides, Antisense; D014746:Vimentin