title: Differential expression of matrix metalloproteinases and proteoglycans in Juvenile Hyaline Fibromatosis.
abstract: BACKGROUND
  Juvenile Hyaline Fibromatosis (JHF) is a rare autosomal recessive disorder, histologically characterized by the production and deposition of an unidentified hyaline material in the skin and other organs. Extracellular matrix molecules are implicated in the development of skin lesion which is debilitating and recurrent and, so far, no treatment is satisfactory.
  
  
  OBJECTIVE
  To investigate the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs) and proteoglycans in lesional as compared to site-matched lesion-free skin tissue specimens of a JHF patient, aiming to elucidate the aetiopathological mechanisms involved in the development of JHF skin lesions.
  
  
  METHODS
  Gelatinase activity of MMP-2 and MMP-9 was investigated by gelatine zymography. Protein levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in skin tissue extracts were measured by ELISA. Gene expression of MMPs, TIMPs and proteoglycans was examined by quantitative RT-PCR.
  
  
  RESULTS
  JHF lesions exhibited significantly higher activity as well as elevated protein and gene expression of MMP-2 and MMP-9, as compared to lesion-free skin tissue specimens. Decorin was downregulated and aggrecan was upregulated in lesional skin, as compared to normal skin.
  
  
  CONCLUSIONS
  The results presented in this study indicate that MMPs and proteoglycans may be involved in the pathogenesis of JHF and therefore these molecules may offer alternative targets for pharmacological intervention to achieve more radical and effective treatment.
authors.affiliation: 2nd Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Greece.
authors.forename: Thrasivoulos G
authors.initials: TG
authors.lastname: Tzellos
authors.forename: Spyros P
authors.initials: SP
authors.lastname: Batzios
authors.forename: Alexander
authors.initials: A
authors.lastname: Dionyssopoulos
authors.forename: George
authors.initials: G
authors.lastname: Karakiulakis
authors.forename: Eleni
authors.initials: E
authors.lastname: Papakonstantinou
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D058578:Biglycan / Q000235:genetics / Q000378:metabolism; D002648:Child; D058575:Decorin / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004792:Enzyme Precursors / Q000378:metabolism; D005109:Extracellular Matrix; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D015870:Gene Expression; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057770:Hyaline Fibromatosis Syndrome / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000201:enzymology* / Q000378:metabolism; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D053674:Aggrecans; D058578:Biglycan; D058575:Decorin; D004792:Enzyme Precursors; D019812:Heparan Sulfate Proteoglycans; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C071927:perlecan; D018093:Gelatinases; C120487:pro-matrix metalloproteinase 9; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9