Relative role of hepatocyte growth factor in mediating epithelial cell-protective effects in lung fibrosis – a role of Bcl-xL induction

Einleitung: Hepatocyte growth factor (HGF) is a cytokine with pleiotropic functions during wound healing and repair. Anti-fibrotic effects have been shown in animal models of lung fibrosis and may be mediated via multiple direct and indirect mechanisms, including promoting endothelial and epithelial cell survival and proliferation and reduction of myofibroblast accumulation. In liver and kidney epithelial cells the increased expression of Bcl-xL protein has been suggested as an important anti-apoptotic mechanism, but it remains to be elucidated in the lung.

Methoden: Main goals of this study are to characterize the expression of Bcl-xL and its cellular localization in lungs from IPF patients in comparison to healthy donors, and to investigate the precise mechanism of HGF-induced prosurvival effect on epithelial cells in vitro and in the bleomycin model of lung fibrosis.

Ergebnisse: Western blot analysis of lung homogenates from IPF subjects showed a significantly increased expression of Bcl-xL protein. IHC analysis forwarded a strong staining in hyperplastic alveolar type II cells and in bronchial epithelial cells. Preliminary in vitro results showed a decreased expression of Bcl-xL in MLE12 cells after Fas ligand-induced apoptosis.

Diskussion: Our results indicate that Bcl-xL may play a role in epithelial repair in IPF. Further studies are needed to show the interaction with the HGF system.