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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1048-1053
Number of pages6
JournalDigestive Diseases and Sciences
Volume53
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • Hepatic stellate cells
  • Liver fibrosis
  • Metalloproteases
  • Ras inhibition

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