The mechanism through which octreotide inhibits hepatic stellate cell activity

Mol Med Rep. 2013 May;7(5):1559-64. doi: 10.3892/mmr.2013.1385. Epub 2013 Mar 20.

Abstract

Hepatic stellate cells (HSCs) are important in the development of liver fibrosis and in the pathogenesis of portal hypertension. Octreotide, an analogue of somatostatin, has been demonstrated to effectively treat fibrosis and portal hypertension; however, its relative mechanism in HSCs remains unknown. LX‑2, the immortalized HSC line, was used to study the mechanism whereby octreotide functions at different concentrations. Real‑time polymerase chain reaction (PCR) and western blot analysis were used to analyze the expression of fibrosis markers and transcription factors following treatment with octreotide. Soluble secreted endothelin‑1 (ET‑1), collagen I and vascular endothelial growth factor (VEGF) were assessed in the supernatants of cultured cells by enzyme-linked immunosorbent assay (ELISA). In the present study, it was shown that octreotide was able to inhibit the proliferative ability of the LX‑2 cells and decrease the expression of transforming growth factor β (TGF‑β), α‑smooth muscle actin (α‑SMA) and smad‑4a. The transcription factors, including c‑Jun and sp‑1, were downregulated in a dose‑dependent manner following treatment with octreotide. The levels of ET‑1 and collagen I in the supernatant decreased significantly in contrast with the normal levels, whereas the levels of VEGF in the LX‑2 cells and the supernatant increased at a high octreotide concentration (10‑5 nM). Octreotide may exert its effects on ET‑1 or other targeting genes in HSCs through the downregulation of c‑Jun and specificity protein 1 (sp‑1), and the increased levels of VEGF may be the reason for the side effects observed at high concentrations of octreotide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cell Line
  • Cell Line, Transformed
  • Cell Proliferation / drug effects
  • Collagen Type I / metabolism
  • Endothelin-1 / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibrosis
  • Hepatic Stellate Cells / drug effects*
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / pathology
  • Humans
  • Hypertension / drug therapy
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Octreotide / pharmacology*
  • Proto-Oncogene Proteins c-jun / antagonists & inhibitors
  • Proto-Oncogene Proteins c-jun / metabolism
  • Smad4 Protein / metabolism
  • Sp1 Transcription Factor / antagonists & inhibitors
  • Sp1 Transcription Factor / metabolism
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Collagen Type I
  • Endothelin-1
  • Proto-Oncogene Proteins c-jun
  • SMAD4 protein, human
  • Smad4 Protein
  • Sp1 Transcription Factor
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Octreotide