Analysis of the cytoprotective effects of Bcl-xL on pulmonary epithelial cell injury

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ObjectiveBcl-xL was first discovered as a molecule related with apoptotic pathway. Recent studies have revealed that it has a cytoprotective effect. However, it remains still unclear whether it is also cytoprotecitve for pulmonary epithelial cells. This research project has been done to clarify this question.Results.1. Bleomycin injured pulmonary epithelial cell MLE15 cells in a dose dependent manner. Knockdown of Bcl-xL expression using a specific siRNA for Bcl-xL increased this pulmonary epithelial cell injury induced by bleomycin.2. Hydrogen peroxide injured MLE15 cells in a dose dependent manner. Knockdown of Bcl-xL expression using a specific siRNA for Bcl-xL increased this pulmonary epithelial cell injury induced by low dose of hydrogen peroxide, but not by high dose of hydrogen peroxide.3. We made lung specific Bcl-xL knockout mice in which Bcl-xL expression in pulmonary epithelial cell is exclusively deficient. These knockout mice grew up normally. Histological studies revealed that lung structure was normal in these knockout mice.Conclusions.These findings demonstrate that Bcl-xL is not necessary for lung development and growth, but that Bcl-xL has cytoprotective effects on pulmonary epithelial cell injury induced by several stress. These results suggest that Bcl-xL in the pulmonary epithelial cells could be a therapeutic strategy for lung injury such as pulmonary fibrosis.