title: Transforming growth factor-β1 regulates the telomerase reverse transcriptase in rat hepatic stellate cells.
abstract: OBJECTIVE
  To determine the effect of transforming growth factor-β1 (TGF-β1) on the expression of telomerase in hepatic stellate cells (HSCs) in rats and the role of TGF-β1 in the development of liver fibrosis.
  
  
  METHODS
  Primary HSCs were isolated from normal rats by density gradient separation and divided into 2 groups for culturing. The morphology of HSCs was identified by the inverted fluorescence microscope. The purity of HSCs was identified by immunohistological expression and fluorescence analysis. One group of HSCs was treated with different concentrations (0, 0.1, 1, and 10 ng/mL) of TGF-β1 for 24 h, while the other group was treated with 1 ng/mL TGF-β1 and cultured for 3, 6, and 9 days. The mRNA expression of telomerase reverse transcriptase (TERT) was assessed and compared by polymerase chain reaction.
  
  
  RESULTS
  Cell morphology showed that TGF-β1 triggered the differentiation of HSCs from a quiescent phenotype into highly activated myofibroblasts. TERT mRNA expression in the primary HSCs showed slight increase with the culture time, though with no statistical difference between the results at various time points (P>0.05). TGF-β1 at 0.1 ng/mL did not significantly affect the TERT mRNA level compared with the 0 ng/mL group, while 1 ng/mL and 10 ng/mL TGF-β1 significantly decreased the level of TERT mRNA (P<0.05). TGF-β1 at 1 ng/mL had only weak effect on TERT mRNA expression after the 3 day treatment compared with the 0 ng/mL group (P>0.05). TGF-β1 at 1 ng/mL significantly inhibited TERT mRNA expression 6 days after the treatment (P<0.05). TGF-β1 inhibited the expression of TERT mRNA level in the HSCs in both dose- and time-dependent manner.
  
  
  CONCLUSIONS
  TGF-β1 may contribute to the transdifferentiation of HSCs by reducing TERT levels to develop hepatic fibrosis.
authors.affiliation: Department of Pharmacy;Department of Cardiology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Yulu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shikun
authors.initials: S
authors.lastname: Liu
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Deng
authors.forename: Lihua
authors.initials: L
authors.lastname: Huang
authors.forename: Zuojun
authors.initials: Z
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D019098:Telomerase / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D019098:Telomerase