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Plasminogen Reduces Lung Fibrosis in the Bleomycin-Induced Lung Fibrosis Model
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A2663 - Plasminogen Reduces Lung Fibrosis in the Bleomycin-Induced Lung Fibrosis Model
Author Block: L. Gagnon, M. Tremblay, B. Grouix, W. Gagnon, A. Felton, P. Laurin; Prometic Biosciences Inc., Laval, QC, Canada.
Rationale: The serine protease plasmin plays a major role in regulating hemostasis through proteolytic degradation of fibrin. Studies using mice lacking the plasmin precursor plasminogen (Plg) have identified additional plasmin functions in inflammation, cell migration, and extracellular matrix degradation that have implications for a variety of pathologic processes. The aim of this study was to investigate the effect of plasminogen in the bleomycin-induced lung fibrosis model.
Methods: Fibrosis was induced in mice by intratracheal instillation of bleomycin (0.007 mg/mouse) on day 0. Murine plasminogen (6 mg/kg) was administered by subcutaneous (sc) injection at day 7, 10, 13, 16, 19 and 23, and vehicle) or pirfenidone (400 mg/kg) or BIBF 1120 (60 mg/kg) were orally administered from day 7 to 27. Mice were euthanized on day 28.
Results: Sc administration of murine plasminogen (6 mg/kg) strongly reduced the percentage of collagen in the inflammatory area in lungs as determined by histomorphometry, while pirfenidone and BIBF 1120 did not reach a significant reduction (p=0.08 and p=0.06, respectively). However, in combination with plasminogen, a significant reduction in the percentage of collagen was observed for both combination. In bronchoalveolar lavage fluid (BALF), PAI-1 was weakly reduced with plasminogen but significantly reduced in the plasminogen/pirfenidone combination while PAI-1 was elevated in the pirfenidone alone group.
Conclusions: These results indicate a direct effect of plasminogen in reduction of lung fibrosis in the bleomycin-induced lung fibrosis model, and may offer the potential as a novel therapy, alone or in combination with pirfenidone or nintedanib, for IPF.
Author Block: L. Gagnon, M. Tremblay, B. Grouix, W. Gagnon, A. Felton, P. Laurin; Prometic Biosciences Inc., Laval, QC, Canada.
Rationale: The serine protease plasmin plays a major role in regulating hemostasis through proteolytic degradation of fibrin. Studies using mice lacking the plasmin precursor plasminogen (Plg) have identified additional plasmin functions in inflammation, cell migration, and extracellular matrix degradation that have implications for a variety of pathologic processes. The aim of this study was to investigate the effect of plasminogen in the bleomycin-induced lung fibrosis model.
Methods: Fibrosis was induced in mice by intratracheal instillation of bleomycin (0.007 mg/mouse) on day 0. Murine plasminogen (6 mg/kg) was administered by subcutaneous (sc) injection at day 7, 10, 13, 16, 19 and 23, and vehicle) or pirfenidone (400 mg/kg) or BIBF 1120 (60 mg/kg) were orally administered from day 7 to 27. Mice were euthanized on day 28.
Results: Sc administration of murine plasminogen (6 mg/kg) strongly reduced the percentage of collagen in the inflammatory area in lungs as determined by histomorphometry, while pirfenidone and BIBF 1120 did not reach a significant reduction (p=0.08 and p=0.06, respectively). However, in combination with plasminogen, a significant reduction in the percentage of collagen was observed for both combination. In bronchoalveolar lavage fluid (BALF), PAI-1 was weakly reduced with plasminogen but significantly reduced in the plasminogen/pirfenidone combination while PAI-1 was elevated in the pirfenidone alone group.
Conclusions: These results indicate a direct effect of plasminogen in reduction of lung fibrosis in the bleomycin-induced lung fibrosis model, and may offer the potential as a novel therapy, alone or in combination with pirfenidone or nintedanib, for IPF.
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