title: Mechanisms of mesenchymal stem cell correction of the impaired biomechanical properties of diabetic skin: The role of miR-29a.
abstract: Diabetic skin has impaired wound healing properties following injury. We have further shown that diabetic skin has weakened biomechanical properties at baseline. We hypothesize that the biomechanical properties of diabetic skin decline during the progression of the diabetic phenotype, and that this decline is due to the dysregulation of miR-29a, resulting in decreased collagen content. We further hypothesize that treatment with mesenchymal stem cells (MSCs) may improve diabetic wound healing by correction of the dysregulated miR-29a expression. We analyzed the biomechanical properties, collagen gene expression, collagen protein production, and miR-29a levels in skin harvested from 6 to 18 week old mice during the development of the diabetic phenotype. We also examined the correction of these impairments by both MSC treatment and the inhibition of miR-29a. Diabetic skin demonstrated a progressive impairment of biomechanical properties, decreased collagen content, and increased miR-29a levels during the development of the diabetic phenotype. MSC treatment decreased miR-29a levels, increased collagen content, and corrected the impaired biomechanical properties of diabetic skin. Additionally, direct inhibition of miR-29a also increased collagen content in diabetic skin. This decline in the biomechanical properties of diabetic skin during the progression of diabetes may increase the susceptibility of diabetic skin to injury and miR-29a appears to play a key role in this process.
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver-Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Carlos
authors.initials: C
authors.lastname: Zgheib
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver-Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Maggie
authors.initials: M
authors.lastname: Hodges
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver-Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Junyi
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: David P
authors.initials: DP
authors.lastname: Beason
authors.affiliation: Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Soslowsky
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver-Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
authors.affiliation: Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver-Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Junwang
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction; D012867:Skin / Q000293:injuries / Q000473:pathology*; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics*; D014947:Wounds and Injuries / Q000235:genetics / Q000473:pathology* / Q000628:therapy
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs