title: Expression of matrix metalloproteinases and their endogenous tissue inhibitors in skin lesions from patients with tuberous sclerosis.
abstract: BACKGROUND
  Tuberous sclerosis complex lesions of the skin may be disfiguring to patients and can only be treated by laser or cosmetic surgery. Clarification of the molecular and structural changes involved in skin hamartomas may unravel targets for pharmacotherapy.
  
  
  OBJECTIVE
  We investigated the expression of matrix metalloproteinase (MMP) and its tissue inhibitor (TIMP) in fibrous plaques, angiofibromas, and lesion-free skin specimens from patients with tuberous sclerosis complex.
  
  
  METHODS
  Gene expression of MMPs and TIMP-1 was measured by reverse transcription polymerase chain reaction, gelatinase activity by gelatin zymography, and the content of collagenases and TIMPs by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Compared with lesion-free specimens, hamartomas exhibited decreased levels of TIMPs and messenger RNA expression of TIMP-1, and increased content of MMP-1 and MMP-13 and activity of MMP-9, although gelatinase gene expression was diminished. Gene expression of MMP-15 and MMP-17 was not affected but was diminished for MMP-14.
  
  
  CONCLUSIONS
  The significant variations of the above extracellular matrix molecules between lesion-free specimens and tuberous sclerosis complex hamartomas overall favors a collagenous protein-degrading microenvironment in affected skin, and argue in support of antiprotease treatment for disfiguring skin lesions.
authors.affiliation: Department of Pharmacology, Aristotle University of Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Papakonstantinou
authors.forename: Alexander
authors.initials: A
authors.lastname: Dionyssopoulos
authors.forename: Alexios J
authors.initials: AJ
authors.lastname: Aletras
authors.forename: Chrisanthi
authors.initials: C
authors.lastname: Pesintzaki
authors.forename: Aristippos
authors.initials: A
authors.lastname: Minas
authors.forename: George
authors.initials: G
authors.lastname: Karakiulakis
mesh_terms: D000328:Adult; D017364:Collagenases / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism; D012867:Skin / Q000201:enzymology*; D014020:Tissue Extracts / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D014402:Tuberous Sclerosis / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D014020:Tissue Extracts; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1