title: Effects of a synthetic retinoid on skin structure, matrix metalloproteinases, and procollagen in healthy and high-risk subjects with diabetes.
abstract: BACKGROUND
  In diabetes, foot ulceration may result from increased skin fragility. Retinoids can reverse some diabetes-induced deficits of skin structure and function, but their clinical utility is limited by skin irritation. The effects of diabetes and MDI 301, a nonirritating synthetic retinoid, and retinoic acid have been evaluated on matrix metalloproteinases (MMPs), procollagen expression, and skin structure in skin biopsies from nondiabetic volunteers and diabetic subjects at risk of foot ulceration using organ culture techniques.
  
  
  METHODS
  Zymography and enzyme-linked immunosorbent assay were utilized for analysis of MMP-1, -2, and -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) and immunohistochemistry for type I procollagen protein abundance. Collagen structure parameters were assessed in formalin-fixed, paraffin-embedded tissue sections.
  
  
  RESULTS
  The % of active MMP-1 and -9 was higher and TIMP-1 abundance was lower in subjects with diabetes. Type 1 procollagen abundance was reduced and skin structural deficits were increased in diabetes. Three μM MDI 301 reduced active MMP-1 and -9 abundance by 29% (P < .05) and 40% (P < .05), respectively, and increased TIMP-1 by 45% (P = .07). MDI 301 increased type 1 procollagen abundance by 40% (P < .01) and completely corrected structural deficit scores. Two μM retinoic acid reduced MMP-1 but did not significantly affect skin structure.
  
  
  CONCLUSIONS
  These data indicate that diabetic patients at risk of foot ulceration have deficits of skin structure and function. MDI 301 offers potential for repairing this skin damage complicating diabetes.
authors: School of Clinical and Experimental Medicine, University of Birmingham, B15 2TT Birmingham, UK.
authors: Wei
authors: W
authors: Zeng
authors: Abd
authors: A
authors: Tahrani
authors: Jayadave
authors: J
authors: Shakher
authors: James
authors: J
authors: Varani
authors: Sharon
authors: S
authors: Hughes
authors: Kiran
authors: K
authors: Dubb
authors: Martin J
authors: MJ
authors: Stevens
mesh_terms: D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017719:Diabetic Foot / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009924:Organ Culture Techniques; D011347:Procollagen / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D012307:Risk Factors; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D006113:United Kingdom / Q000453:epidemiology
chemical_list: C488463:MDI 301; D061965:Matrix Metalloproteinase Inhibitors; D011347:Procollagen; D011480:Protease Inhibitors; D020033:Protein Isoforms; D012176:Retinoids; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1