Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Sep 7, 2008; 14(33): 5186-5191
Published online Sep 7, 2008. doi: 10.3748/wjg.14.5186
Phosphatidylinositol 3-kinase/Akt pathway regulates hepatic stellate cell apoptosis
Yan Wang, Xiao-Yu Jiang, Li Liu, Hui-Qing Jiang
Yan Wang, Li Liu, Hui-Qing Jiang, Department of Gastroenterology, The Second Hospital of Hebei Medical University, The Hebei Institute of Gastroenterology, Shijiazhuang 050000, Hebei Province, China
Xiao-Yu Jiang, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
Author contributions: Jiang HQ, Liu L, and Wang Y designed the research; Wang Y and Jiang XY performed the research; Wang Y analyzed data; and Jiang HQ, Liu L, Wang Y and Jiang XY wrote the paper.
Supported by (in part) The Natural Science Foundation of Hebei Province, China, No.C2007000843
Correspondence to: Hui-Qing Jiang, MD, PhD, Department of Gastroenterology, The Second Hospital of Hebei Medical University, The Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang 050000, Hebei Province, China.
Telephone: +86-311-66002955 Fax: +86-311-87061012
Received: May 6, 2008
Revised: August 13, 2008
Accepted: August 20, 2008
Published online: September 7, 2008

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.

Keywords: Hepatic fibrosis, Hepatic stellate cells, Phosphatidylinositol 3-kinase, Akt, Cell apoptosis