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10.1038/labinvest.2011.80

http://scihub22266oqcxt.onion/10.1038/labinvest.2011.80
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C5683845!5683845!21577212
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suck abstract from ncbi


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pmid21577212      Lab+Invest 2011 ; 91 (8): 1206-18
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  • Absence of Thy-1 results in TGF-? induced MMP-9 expression and confers a profibrotic phenotype to human lung fibroblasts #MMPMID21577212
  • Ramírez G; Hagood JS; Sanders Y; Ramírez R; Becerril C; Segura L; Barrera L; Selman M; Pardo A
  • Lab Invest 2011[Aug]; 91 (8): 1206-18 PMID21577212show ga
  • Fibroblasts differ in a variety of phenotypic features, including the expression of Thy-1 a glycophosphatidylinositol-linked glycoprotein. Fibroblasts in idiopathic pulmonary fibrosis (IPF) are Thy-1-negative, while most fibroblasts from normal lungs are Thy-1-positive. However, the functional consequences of the absence of Thy-1 are not fully understood. We analyzed the expression of Thy-1 in several primary fibroblasts lines derived from IPF, hypersensitivity pneumonitis (HP), and normal human lungs. We found that a high proportion, independently of their origin, expressed Thy-1 in vitro. We identified a primary culture of HP fibroblasts which did not express Thy-1, and compared several functional activities between Thy-1(?) and Thy-1(+) fibroblasts. Thy-1(?) fibroblasts were smaller (length: 41.3±20.8? versus 83.1±40?), showed increased proliferative capacity and enhanced PDGF-induced transmigration through collagen I (59.9% versus 42.2% over control under basal conditions, p<0.01). Likewise, Thy-1(?) fibroblasts either spontaneously or after TGF-? stimulation demonstrated stronger contraction of collagen matrices (e.g. 0.17±0.03 versus 0.6±0.05 cm2 after TGF- stimulation at 24 h; p<0.01). Thy-1(?) lung fibroblasts stimulated with TGF-?1 expressed MMP-9, an enzyme that is usually not produced by lung fibroblasts. TGF?-induced MMP-9 expression was reversible upon re-expression of Thy-1 after transfection with full-length Thy-1. ?-glycan, a TGF-? receptor antagonist abolished MMP-9 expression. TGF-?1-induced MMP-9 in Thy-1(?) fibroblasts depended on the activation of ERK1/2 signalling pathway. Finally, we demonstrated that fibroblasts from IPF fibroblastic foci which do not express Thy-1 exhibit strong staining for immunoreactive MMP-9 protein in vivo. These findings indicate that loss of Thy-1 in human lung fibroblasts induces a fibrogenic phenotype.
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