Digestive Diseases and Sciences

, Volume 53, Issue 4, pp 1048–1053 | Cite as

The Effect of Ras Inhibition on the Proliferation, Apoptosis and Matrix Metalloproteases Activity in Rat Hepatic Stellate Cells

  • Isabel Zvibel
  • Dan Bar-Zohar
  • Yoel Kloog
  • Ran Oren
  • Shimon Reif
Original Paper


In vivo inhibition of Ras by its antagonist farnesylthiosalicylic acid (FTS) prevents and reverses liver fibrosis in a rat model. In this study we showed the in vitro effects of Ras inhibition in a rat hepatic stellate cell line, HSC-T6. The IC50 of FTS that inhibited PDGF-induced proliferation was 15 μM. FTS, by itself or in combination with PDGF, induced a three- to fivefold increase in the number of apoptotic stellate cells but did not induce apoptosis in cells cultured with TGFβ1. We observed increased activity of MMP-9 and MMP-2 induced by FTS in combination with PDGF or TGFβ. FTS, alone or in the presence of PDGF and TGFβ, reduced collagen I mRNA expression. In conclusion, the in vivo amelioration of liver fibrosis by FTS may be explained by its ability to inhibit hepatic stellate cell proliferation, induce apoptosis and MMP-2 and MMP-9 activity, and decrease collagen I expression.


Hepatic stellate cells Liver fibrosis Ras inhibition Metalloproteases 


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Isabel Zvibel
    • 1
  • Dan Bar-Zohar
    • 2
  • Yoel Kloog
    • 3
  • Ran Oren
    • 1
  • Shimon Reif
    • 4
  1. 1.Gastroenterology InstituteTel Aviv Sourasky Medical CenterTel AvivIsrael
  2. 2.Department of Surgery BTel Aviv Sourasky Medical CenterTel AvivIsrael
  3. 3.Department of NeurobiochemistryTel Aviv UniversityTel AvivIsrael
  4. 4.Department of Pediatric Gastroenterology, Dana Children HospitalTel Aviv Sourasky Medical CenterTel AvivIsrael

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