Details

Autor(en) / Beteiligte

• Shetty, Shwetha Kumari

Titel

Regulation of Bleomycin-induced Lung Epithelial Injury by p53 Interaction with the Fibrinolytic System

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2011

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Lung epithelial cell (LEC) apoptosis and alveolar fibrin deposition are two major events associated with acute lung injury and the development of progressive pulmonary fibrosis. Alveolar fibrin deposition and disruption of fibrin turnover during acute lung injury, has been attributed to altered expression of urokinase type plasminogen activator (uPA), the uPA receptor (uPAR) and uPA inhibitor, PAI-1. Bleomycin-induced lung epithelial cell apoptosis involves induction of tumor suppressor protein p53 due to DNA damage. This in turn inhibits uPA, uPAR and induces PAI-1 expression in lung epithelial cells. In this study changes in the lung epithelial cell p53, uPA, uPAR and PAI-1 is determined by western blotting and immunohistochemical analyses of the tissue sections. Apoptosis is assessed by flow cytometry and TUNEL staining. Inhibition of bleomycin induced LEC p53 by Colrid-1 reverses suppression of uPA and uPAR, inhibits PAI-1-1 and prevents LEC apoptosis. Local and systemic administration of Colrid-1 markedly attenuates bleomycin-induced LEC apoptosis and pulmonary fibrosis in vivo.