MMP-7 knock-in corneal fibroblast cell lines secrete MMP-7 with proteolytic activity towards collagen XVIII

Curr Eye Res. 2010 Sep;35(9):799-805. doi: 10.3109/02713683.2010.494239.

Abstract

Purpose: To determine whether matrix metalloproteinase-7 (MMP-7) that is stably overexpressed by mouse corneal fibroblast cell lines exhibits proteolytic activity against the NC1 fragment of collagen XVIII.

Methods: Corneal fibroblasts isolated from MMP-7 knockout (7ko) mice were subjected to SV40 T-antigen immortalization and stably transfected with a bicistronic retroviral vector encoding green fluorescence protein and active MMP-7. The resulting MMP-7 knock-in fibroblasts (7ko-MMP-7 cells) were isolated and enriched by fluorescence activated cell sorting (FACS). Culture media samples from 7ko and 7ko-MMP-7 cells were then incubated with the recombinant NC1 fragment of collagen XVIII, and NC1 degradation was monitored by immunoblotting.

Results: Immunoblot analysis revealed that MMP-7 was present in lysates and culture media from 7ko-MMP-7 fibroblasts, but not media from immortalized 7ko fibroblasts. Importantly, lower amounts of the NC1 fragment were present in in vitro enzymatic reaction mixtures containing concentrated 7ko-MMP-7 media than in those containing concentrated 7ko media.

Conclusion: Immortalized fibroblasts stably transfected with MMP-7 secrete active MMP-7 with proteolytic activity towards the NC1 fragment of collagen XVIII.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Cell Line
  • Collagen Type XVIII / metabolism*
  • Cornea / enzymology*
  • Fibroblasts / enzymology*
  • Flow Cytometry
  • Gene Expression Regulation, Enzymologic / physiology*
  • Gene Knock-In Techniques
  • Genetic Vectors
  • Matrix Metalloproteinase 7 / genetics*
  • Matrix Metalloproteinase 7 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Polymerase Chain Reaction
  • Retroviridae / genetics
  • Transfection

Substances

  • Antigens, Polyomavirus Transforming
  • Collagen Type XVIII
  • Matrix Metalloproteinase 7