title: [Dynamic changes of MMP-1, MMP-9 and TIMP-1 in the refractory diabetic dermal ulcers treated by autologous Platelet-rich gel].
abstract: OBJECTIVE
  To investigate the dynamic changes of matrix metalloproteinase-1,-9 (MMP-1, MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1 ) in the refractory diabetic dermal ulcers treated with autologous platelet-rich gel (APG).
  
  
  METHODS
  86 patients with nonhealing diabetic dermal ulcers were randomly assigned to two groups treated with standard procedures and APG (standard care plus topic application of autologous platelet-rich gel). The granulation tissues were collected at d0, d3, d6, d9, and d15 in patients in the APG group and at d0, d6, d15 in patients in the standard care group. The areas of ulcers were measured. The protein levels of MMP-1, MMP-9 and TIMP-1 in the tissues were determined with ELISA. The ratio of MMP-9/TIMP-1 and its relationship with the areas of ulcers were examined.
  
  
  RESULTS
  The areas of ulcers of patients in the APG group decreased significantely (vs. do, P < 0.05). The concentrations of MMP-1 in the granulation tissues of patients treated with APG fluctuated and reached the lowest level at d15 (vs. d6, P < 0.05). The concentrations of MMP-9 in the patients treated with AGP decreased from d3 to d15, but without statistical significance compared with d0 (P > 0.05). The concentrations of TIMP-1 in the patients treated with AGP increased from d3 and reached the peak at d6 (P < 0.05). The ratio of MMP-9/TIMP-1 at both d6 and d15 decreased significantly compared with d0 (P < 0.05) in the patients treated with AGP. The areas of ulcers in the patients with standard care decreased significantly at d15 (vs. d6, P < 0.05). The concentrations of MMP-1 reached the peak at d6 (P < 0.05) and then decreased in the patients with standard care but was still higher than the patients treated with APG (P < 0.05). The concentrations of MMP-9 decreased significantly at d15 compared with d0 in the patients treated with standard care (P < 0.05), but the change of TIMP-1 was not significant. The ratio of MMP-9/TIMP-1 in the patients with standard care decreased at d15 compared with the d0 (P < 0.05). The ratio of MMP-9/TIMP-1 was positively correlated with the areas of ulcers (r = 0.353, P < 0.05).
  
  
  CONCLUSIONS
  Topical application of APG might redress the proteolytic imbalance of refractory diabetic dermal ulcers by decreasing the concentration of MMPs and increasing that of TIMPs in granulation tissues. The ratio of MMP-9/TIMP-1 is a predictor of poor healing of refractory diabetic dermal ulcers.
authors.affiliation: Diabetic Foot Care Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: He
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Chen
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Li
authors.forename: Xing-wu
authors.initials: XW
authors.lastname: Ran
mesh_terms: D000328:Adult; D000368:Aged; D017364:Collagenases / Q000378:metabolism*; D048909:Diabetes Complications / Q000378:metabolism / Q000628:therapy*; D017719:Diabetic Foot / Q000378:metabolism / Q000628:therapy*; D005260:Female; D005782:Gels; D006097:Granulation Tissue / Q000378:metabolism; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D017713:Platelet Transfusion / Q000379:methods; D053657:Platelet-Rich Plasma; D012883:Skin Ulcer / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014945:Wound Healing
chemical_list: D005782:Gels; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1