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Matrix metalloproteinase2 (MMP2) maintains barrier function
Author(s) -
Garg Pallavi,
Robbins Hilary C,
Epstein Steven,
Ravi Anupama,
Merlin Didier
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a585-d
Subject(s) - mmp2 , barrier function , matrix metalloproteinase , western blot , paracellular transport , tight junction , downregulation and upregulation , transfection , microbiology and biotechnology , chemistry , inflammation , claudin , mmp9 , biology , permeability (electromagnetism) , immunology , biochemistry , gene , membrane
Background and Significance: The matrix metalloproteinase MMP2 is upregulated during human as well as animal models of inflammatory bowel disease. We recently demonstrated that epithelial‐derived MMP2 mediates protective effect during inflammation and tissue damage in colitis. In this study, we examined the potential mechanism by which MMP‐2 exerts its protective effect. Methods: Permeability assays were done using FITC‐dextran in wild type and MMP‐2 null mice. Stably transfected Caco2BBE cells with pEGFP plasmid with and without MMP2 gene were used to study permeability assay, transepithelial resistance (TER), and tight junction proteins. Western blot and immunofluoroscence were used to examine distribution of tight junction proteins. Results: Overexpressed MMP2 showed decreased paracellular flux of both 4 and 40 kD FITC dextran as well as increased TER compared to vector. There was a decrease in paracellular flux by 70% and 50% of both 4 and 40 kD FITC dextran, respectively among overexpressed MMP‐2 compared to vector, while the increase of TER was 34% compared to vector. Claudin‐1,‐2 and ‐5 were significantly upregulated in cells overexpressing MMP‐2 while there was no change in the expression of claudin‐4. Summary and conclusions: Together, our data suggest that MMP2 plays an important role in maintenance of epithelial barrier function. Thus during inflammation, wherein MMP‐2 protein and activity is highly upregulated, epithelial‐derived MMP‐2 may be a critical host factor involved in protecting host from luminal pathogens and toxins.