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- Title
Tumor necrosis factor-alpha-stimulated membrane type 1-matrix metalloproteinase production is modulated by epidermal growth factor receptor signaling in human gingival fibroblasts.
- Authors
Smith PC; Guerrero J; Tobar N; Cáceres M; González MJ; Martínez J
- Abstract
Background and Objectives: Membrane type 1-matrix metalloproteinase (MT1- MMP) is a collagenolytic enzyme involved in connective tissue remodeling. In periodontal tissues, either cytokines or growth factors regulate the production of proteolytic enzymes. Mice deficient in epidermal growth factor receptor (EGFR) show a reduced expression of MT1-MMP, suggesting that this receptor may play an important role in MT1-MMP production. The present study evaluated the role of the inflammatory cytokine tumor necrosis factor-a (TNF-a) and EGFR in the production of MT1-MMP in gingival fibroblasts. Material and Methods: Primary cultures of human gingival fibroblasts were cultured over plastic or a type I collagen matrix and stimulated with TNF-a and EGF. A selective EGFR inhibitor (AG1478) was used to interfere with this signaling pathway. Production of MT1-MMP and activation of proMMP-2 were studied using Western blot and gelatin zymography, respectively. Activation of EGFR signaling was assessed through immunoprecipitation and Western blot. Expression of EGFR ligands was determined through reverse transcriptase-polymerase chain reaction. Results: Treatment of gingival fibroblasts cultured over a collagen matrix with TNF-a stimulated proMMP-2 activation and MT1-MMP production. However, after using AG1478, both responses were inhibited. Tumor necrosis factor-a induced EGFR transactivation and stimulated the expression of the mRNA for the EGFR ligands heparin binding-epidermal growth factor (HB-EGF) and transforming growth factor-a (TGF-a).
- Publication
Journal of Periodontal Research, 2009, Vol 44, Issue 1, p73
- ISSN
0022-3484
- Publication type
Journal Article
- DOI
10.1111/j.1600-0765.2007.01081.x