title: Cyclosporine A Downregulates MMP-3 and MMP-13 Expression in Cultured Pterygium Fibroblasts.
abstract: OBJECTIVE
  To investigate the regulation of matrix metalloproteinase (MMP)-3 and MMP-13 expression over time and in the presence of cyclosporine A (CsA) in primary cultured human pterygium fibroblasts. We also examined the effects of CsA on cultured human pterygium fibroblasts.
  
  
  METHODS
  Primary cultured human pterygium fibroblasts subjected to scratch assays were exposed to 1 and 100 µg/mL of CsA for 3 or 10 minutes. Cells were washed with Dulbecco phosphate-buffered saline, and then incubated with serum-depleted Dulbecco modified Eagle medium/F-12 medium for 48 hours. Expression levels of MMP-3 and MMP-13 proteins and the corresponding mRNA transcripts were determined by western blotting and reverse transcription polymerase chain reaction assays, respectively.
  
  
  RESULTS
  Migration of cultured pterygium fibroblast cells was suppressed by pretreatment with CsA compared with controls in a time-dependent and dose-dependent manner (3 minutes, 50.6% ± 1.1 in 1 µg/mL, 60.0% ± 1.2 in 100 µg/mL; 10 minutes, 59.8% ± 5.7 in 1 µg/mL, 60.5 ± 2.4 in 100 µg/mL, respectively, P < 0.01). Pretreatment with CsA also reduced the mRNA (P < 0.05) and protein expression levels (P < 0.05).
  
  
  CONCLUSIONS
  CsA was actively involved in the migration of pterygium fibroblasts. Cell migration is inhibited in response to CsA through the inhibition of MMP-3 and MMP-13 expression. These findings reveal the therapeutic potential of CsA on pterygium progression. Further studies will be necessary to elucidate the precise intracellular signal mechanism responsible for CsA-induced downregulation of MMPs in pterygium fibroblasts.
authors.affiliation: *Cheil Eye Research Institute, Cheil Eye Hospital, Daegu, Republic of Korea; and †Developmental Biology Laboratory, Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Yeoun-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae-Chang
authors.initials: JC
authors.lastname: Jung
authors.forename: Soon-Young
authors.initials: SY
authors.lastname: Jung
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Kyoo Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Young Jeung
authors.initials: YJ
authors.lastname: Park
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D011625:Pterygium / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3