title: Blood glucose fluctuation affects skin collagen metabolism in the diabetic mouse by inhibiting the mitogen-activated protein kinase and Smad pathways.
abstract: BACKGROUND
  We recently reported that in mice, blood glucose fluctuations (BGF) produced more detrimental effects on skin structure and function than did diabetes alone.
  
  
  OBJECTIVE
  To determine whether treatment of BGF changes the collagen metabolism in the skin of diabetic mice, and to explore its possible molecular mechanism further.
  
  
  METHODS
  The study used diabetic and BGF animal models. Immunohistochemistry, western blotting and real-time PCR analysis were used to detect the expression of type I collagen, matrix metalloproteinase (MMP)-1, MMP-2 and MMP-13, tissue inhibitor of metalloproteinase (TIMP)-1, extracellular signal-regulated kinase, p38, and Smad2/3. The activities of mitogen-activated protein kinase (MAPK) and Smad signal molecules were also detected by western blotting, and the skin fibroblast ultrastructure was examined using an electron microscope.
  
  
  RESULTS
  BGF treatment produced a twofold reduction in type I collagen synthesis compared with diabetes-only mice. Expression of MMP-1, MMP-2 and MMP-13 increased markedly in the BGF-treated mice, but TIMP-1 expression was strongly downregulated by the BGF treatment. There was also evidence of higher levels of apoptosis of skin fibroblasts after BGF treatment.
  
  
  CONCLUSIONS
  BGF treatment can affect collagen production in the skin of diabetic BGF mice by inhibiting collagen synthesis and increasing collagen degradation. Furthermore, both MAPK and Smad signalling pathways seem to play a role in the inhibition of collagen production in diabetic mice treated with BGF.
authors.affiliation: Institute of Biomedicine, School of Life Science, East China Normal University, Shanghai, China. xyye@bio.ecnu.edu.cn
authors.forename: X
authors.initials: X
authors.lastname: Ye
authors.forename: X
authors.initials: X
authors.lastname: Cheng
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Dang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D024042:Collagen Type I; D051785:Smad Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019950:Mitogen-Activated Protein Kinase 1; D020782:Matrix Metalloproteinases