title: Differential gene expression of MMP-1, TIMP-1 and HGF in clinically involved and uninvolved skin in South Africans with SSc.
abstract: OBJECTIVE
  To investigate the differential expression of MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1) and hepatocyte growth factor (HGF) in clinically involved (affected) and uninvolved (unaffected) skin in patients with SSc.
  
  
  METHODS
  Punch biopsies from affected forearm and unaffected upper back skin of 16 black South Africans with dcSSc and skin samples of 15 ethnically matched healthy controls were studied. Quantitative mRNA expression of MMP-1, TIMP-1 and HGF was performed by relative reverse transcription quantitative PCR.
  
  
  RESULTS
  Compared with controls, TIMP-1 expression was significantly upregulated in patients, a 796- and 397-fold difference for affected and unaffected skin (P < 0.00001 for both), respectively. Conversely, MMP-1 expression was significantly decreased in patients, a 10- and 12.5-fold difference for affected and unaffected skin (P = 0.0004 for both), respectively. HGF expression was up-regulated in both affected and unaffected skin, a 14- and 18-fold difference (P = 0.004 and P = 0.002), respectively. Within the patient group, HGF expression in affected skin of patients correlated significantly with the European scleroderma disease activity score (r = 0.60, P = 0.013).
  
  
  CONCLUSIONS
  Perturbations in gene expression of TIMP-1, MMP-1 and HGF were evident in both affected and unaffected skin of the dcSSc patients. Targeting TIMP-1, which showed the greatest dysregulation, needs to be explored as a way of reducing collagen deposition and fibrosis in dcSSc.
authors.affiliation: Division of Rheumatology, Faculty of Health Sciences, Chris Hani Baragwanath Academic Hospital, P.O. Bertsham 2013, South Africa.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Frost
authors.forename: Michèle
authors.initials: M
authors.lastname: Ramsay
authors.forename: Ridwan
authors.initials: R
authors.lastname: Mia
authors.forename: Laeeka
authors.initials: L
authors.lastname: Moosa
authors.forename: Eustasius
authors.initials: E
authors.lastname: Musenge
authors.forename: Mohammed
authors.initials: M
authors.lastname: Tikly
mesh_terms: D000328:Adult; D001706:Biopsy; D044383:Black People / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012879:Skin Physiological Phenomena; D013019:South Africa; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D055815:Young Adult
chemical_list: C066855:HGF protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D017228:Hepatocyte Growth Factor; D003094:Collagen; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1