title: Regulatory Effects and Mechanism of Adenovirus-Mediated PTEN Gene on Hepatic Stellate Cells.
abstract: BACKGROUND
  Tension homology deleted on chromosome ten (PTEN) is important in liver fibrosis.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the PTEN gene effects and mechanism of action on hepatic stellate cells (HSCs).
  
  
  METHODS
  The rat primary HSCs and human LX-2 cells were transfected by an adenovirus containing cDNA constructs encoding the wild-type PTEN (Ad-PTEN), the PTEN mutant G129E gene (Ad-G129E) and RNA interference targeting the PTEN sequence PTEN short hairpin RNA (PTEN shRNA), to up-regulate and down-regulate PTEN expression, respectively. The HSCs were assayed with a fluorescent microscope, real time PCR, Western blot, MTT, flow cytometry and Terminal-deoxynucleoitidyl transferase mediated nick end labeling. In addition, the CCl4 induced rat hepatic fibrosis model was also established to check the in vivo effects of the recombinant adenovirus with various levels of PTEN expression.
  
  
  RESULTS
  The data have shown that the over-expressed PTEN gene led to reduced HSCs activation and viability, caspase-3 activity and cell cycle arrest in the G0/G1 and G2/M phases, as well as negative regulation of the PI3K/Akt and FAK/ERK signaling pathways in vitro. The over-expressed PTEN gene improved liver function, inhibited proliferation and promoted apoptosis of HSCs both in vitro and in vivo.
  
  
  CONCLUSIONS
  These data have shown that gene therapy using the recombinant adenovirus encoding wild-type PTEN inhibits proliferation and induces apoptosis of HSCs, which is a potential treatment option for hepatic fibrosis.
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.
authors.forename: Shurui
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Huo
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 215 West Heping Road, Shijiazhuang, 050000, Hebei, China. xiaolanzh@126.com.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D015316:Genetic Therapy; D055166:Hepatic Stellate Cells / Q000502:physiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D002251:Carbon Tetrachloride; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487216:Pten protein, rat; D053148:Caspase 3
keywords: Gene therapy; Hepatic fibrosis; Hepatic stellate cell; PTEN