title: The influence of elastin degradation products, glucose and atorvastatin on metalloproteinase-1, -2, -9 and tissue inhibitor of metalloproteinases-1, -2, -3 expression in human retinal pigment epithelial cells.
abstract: OBJECTIVE
  Hyperglycemia and increased concentrations of elastin degradation products (EDPs) are common findings in patients with diabetes, atherosclerosis and hypertension. The aim of this study was to assess the influence of high glucose, EDPs and atorvastatin on MMP-1, MMP-2, MMP-9 and TIMP1-3 gene expression in human retinal pigment epithelial cells (HRPE) in vitro.
  
  
  METHODS
  HRPE were cultured for 24 hours with the substances being tested (glucose, EDPs), alone or in combination. Additionally, the cells were treated with atorvastatin in two different concentrations (1 or 10 μM). After incubation, total cellular RNA was extracted and used for gene expression evaluation. Gene expression was measured using the real-time RT-PCR technique.
  
  
  RESULTS
  Glucose, EDPs and atorvastatin had no impact on TIMP-1 and TIMP-3 expression. HRPE cells treated with glucose or EDPs with the addition of atorvastatin had a statistically significant decrease of TIMP-2 expression; glucose alone decreased MMP-1 expression. Atorvastatin decreased expression of all assessed genes, except TIMP-1 and TIMP-3 in a dose-dependent manner.
  
  
  CONCLUSIONS
  Our results confirm the importance of MMPs and TIMPs in retinal vascular biology. Atorvastatin-induced MMPs gene expression can deeply affect extracellular matrix turnover, which may play an important role in the progression of ocular diseases.
authors.affiliation: Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Dorecka
authors.affiliation: Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Francuz
authors.affiliation: Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Garczorz
authors.affiliation: Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Siemianowicz
authors.affiliation: Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Wanda
authors.initials: W
authors.lastname: Romaniuk
mesh_terms: D000069059:Atorvastatin; D002460:Cell Line; D004549:Elastin / Q000737:chemistry; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D059748:Proteolysis; D011758:Pyrroles / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D006538:Heptanoic Acids; D010446:Peptide Fragments; D011758:Pyrroles; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2; D004549:Elastin; D000069059:Atorvastatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D005947:Glucose