title: Impaired biomechanical properties of diabetic skin implications in pathogenesis of diabetic wound complications.
abstract: Diabetic skin is known to have deficient wound healing properties, but little is known of its intrinsic biomechanical properties. We hypothesize that diabetic skin possesses inferior biomechanical properties at baseline, rendering it more prone to injury. Skin from diabetic and nondiabetic mice and humans underwent biomechanical testing. Real-time PCR was performed for genes integral to collagen synthesis and degradation. MMP-2 and MMP-9, and TIMP-1 protein levels were assessed by ELISA and zymography. Collagen I and III content was assessed using Western blot analysis. At baseline, both murine and human diabetic skin was biomechanically inferior compared to nondiabetic skin, with decreased maximum stress and decreased modulus (P < 0.001 and < 0.05, respectively). Surprisingly, the expression of genes involved in collagen synthesis were significantly up-regulated, and genes involved in collagen degradation were significantly down-regulated in murine diabetic skin (P < 0.01). In addition, MMP-2 and MMP-9/TIMP-1 protein ratios were significantly lower in murine diabetic skin (P < 0.05). Collagen I levels and I:III ratios were lower in diabetic skin (P < 0.05). These findings suggest that the predisposition of diabetics to wounds may be the result of impaired tissue integrity at baseline, and are due, in part, to a defect in the regulation of collagen protein synthesis at the post-transcriptional level.
authors.affiliation: Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Dustin M
authors.initials: DM
authors.lastname: Bermudez
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Herdrich
authors.forename: Junwang
authors.initials: J
authors.lastname: Xu
authors.forename: Robert
authors.initials: R
authors.lastname: Lind
authors.forename: David P
authors.initials: DP
authors.lastname: Beason
authors.forename: Marc E
authors.initials: ME
authors.lastname: Mitchell
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Soslowsky
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism* / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D004548:Elasticity; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9