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Matrix metalloproteinase‐19 deficient fibroblasts display a profibrotic phenotype (1046.4)
Author(s) -
Pardo Annie,
Jara Paul,
Calyeca Jazmin,
Romero Yair,
Placido Luis,
Yu Guoying,
Maldonado Vilma,
Selman Moises
Publication year - 2014
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.28.1_supplement.1046.4
Subject(s) - fibroblast , idiopathic pulmonary fibrosis , extracellular matrix , myofibroblast , pulmonary fibrosis , bleomycin , matrigel , fibrosis , downregulation and upregulation , matrix metalloproteinase , type i collagen , lung , chemistry , cancer research , endocrinology , pathology , medicine , biology , microbiology and biotechnology , in vitro , angiogenesis , biochemistry , chemotherapy , gene
Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal interstitial lung disease of unknown etiology characterized by aberrant activation of epitelial cells that induce the migration, proliferation and activation of fibroblast/myofibroblasts. The resulting distinctive fibroblastic foci are responsible of the excessive extracellular matrix production. We have recently found that Mmp19‐/‐ mice develop an exaggerated bleomycin‐induced lung fibrosis but the mechanisms are unclear. In this study we explored the effect of MMP19 deficiency on fibroblast behavior. Compared with wild type mice, Mmp19‐/‐ lung fibroblasts showed a decreased expression of Th1‐1 (p<0.01), and alpha 1 (I) collagen gene and collagen protein production at baseline and after TGF‐β treatment (p< 0.05). Likewise, they showed a significant increase in growth rate (p< 0.01), and in transmigration over Boyden chambers coated with type I collagen or with Matrigel (p< 0.05). Microarray analysis revealed the upregulation of several profibrotic pathways in Mmp19‐/‐ lung fibroblasts. These findings suggest that the absence of MMP19 induces in lung fibroblasts a profibrotic phenotype. Grant Funding Source : CONACyT 177641