Phosphatidylinositol 3-kinase/Akt pathway regulates hepatic stellate cell apoptosis.

AIM To investigate the role of phosphatidylinositol 3-kinase (PI 3-K)/Akt signaling pathway in the balance of HSC activation and apoptosis in rat hepatic stellate cells (HSC). METHODS An activated HSC cell line was used in this study. LY 294002, the PI 3-K/Akt signal pathway blocker was used to investigate the molecular events on apoptosis in HSC and to interpret the role of this pathway in HSC apoptosis. Immunocytochemistry, Western blot and reverse transcription polymerase chain reaction (RT-PCR) analysis were applied to detect the expression of PI 3-K, and simultaneously phosphorylated-Akt (p-Akt) and total-Akt were determined by Western blot. The HSC apoptosis was examined by annexin-V/propidium iodide double-labelled flow cytometry and transmission electron microscopy. RESULTS The apoptosis rates in LY 294002 (30.82%+/-2.90%) and LY 294002+PDGF-BB (28.16%+/-2.58%) groups were significantly increased compared with those of control (9.02%+/-1.81%) and PDGF-BB (4.35%+/-1.18%). PDGF-BB augmented PI 3-K and p-Akt expression. LY 294002 significantly reduced the contents of PI 3-K and p-Akt. mRNA transcription evaluated by RT-PCR showed similar tendencies as protein expression. CONCLUSION Inhibition of PI 3-K/Akt signaling pathway induces apoptosis in HSC.

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