title: Type I collagen accelerates the spreading of lens epithelial cells through the expression and activation of matrix metalloproteinases.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) are involved in posterior capsule opacification (PCO), but the mechanisms that promote MMP expression are yet to be determined. In this study, we investigated whether type I collagen, which is only detected in aged or cataractous lens capsules, affects the expression and activation of MMPs in primary-cultured chicken lens epithelial cells (LECs).
  
  
  METHODS
  Chicken LECs were isolated from chicken embryos and cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum (FBS) on type I collagen-coated dishes. The activity of secreted MMPs was examined using gelatin zymography, and cell spreading was determined as the average area of randomly distributed cells. For some experiments, LECs were cultured in the presence of the broad-spectrum MMP inhibitor, GM6001. LECs cultured on uncoated dishes were used as controls. To examine the involvement of MMP in cell migration, a wound-healing assay was performed in the presence of the MMP inhibitor.
  
  
  RESULTS
  Chicken LECs constitutively express the pro-form of MMP-2. When LECs were cultured on type I collagen-coated dishes, they expressed the active form of MMP-2 and the pro-form of MMP-9. This expression and activation by type I collagen was also observed in the human LEC line SRA-01/04, but not the human Müller glial cell line, MIO-M1. Type I collagen enhanced cell spreading, which was suppressed by the MMP inhibitor. Type I collagen also accelerated α-smooth muscle actin expression. In addition, LEC migration was inhibited by the MMP inhibitor in a dose-dependent manner in the wound-healing assay.
  
  
  CONCLUSIONS
  Type I collagen promotes the expression and activation of MMPs in a LEC-specific manner. These results suggest that type I collagen may play a role in PCO development.
authors.affiliation: Faculty of Pharmaceutical Science, Teikyo University , Itabashi-ku, Tokyo , Japan.
authors.forename: Arata
authors.initials: A
authors.lastname: Shimada
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kosano
mesh_terms: D000818:Animals; D002386:Cataract / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D024042:Collagen Type I / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D057852:Posterior Capsule of the Lens / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D024042:Collagen Type I; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9