Role of MAPK and PI3K pathways in hepatocyte growth factor-mediated anti-apoptosis
Objective To investigate the role of MAPK, PI3K/AKT pathways in HGF dependent protected effect on ActD/TNF-α induced apoptosis in a liver stem like cell line WB F-344 cells. Methods WB cell were exposed to ActD, TNF-α or/and HGF. Apoptosis were evaluated by flow cytometry (FCM) and DNA fragmentation; the phospho-MAPK were detected by Western blot. Results The results show that ActD/TNF-α can induced apoptosis in WB F-344 cells, but TNF-α does not induce a significant apoptosis alone. The apoptosis is detected at 9 h after adding ActD/TNF-α and achieves the peak at 48 h. Furthermore, we find that HGF can significantly reduce the apoptosis of WB cell induced by ActD/TNF-α and it enhanced with increase of HGF concentration. Our results also show that the anti-apoptosis effects of HGF are inhibited when PI3k pathway is abolished by the specific inhibitor Wartmanner, but not inhibited when MAPK pathway is abolished by inhibitor U0126. Conclusion Apoptosis of WB cells can be induced by ActD/TNF-α, and HGF can protect the WB cells from ActD/TNF-α induced apoptosis. Although HGF can activate both the PI3K and MAPK pathways, the anti-apoptosis effect of HGF occurs via a PI3K pathway and is not dependent on the MAPK pathway.