Inhibition of the activation of hepatic stellate cells by arundic acid via the induction of cytoglobin

Abstract

Background: The activation of hepatic stellate cells plays a central role in the development of liver fibrosis during chronic liver trauma. The aim of the present study was to identify a compound that inhibits the activation process of stellate cells.

Methods: Rat primary cultured stellate cells and a human stellate cell line (LX-2) were used. The effects of arundic acid on the expression of α-smooth muscle actin, collagen 1α1, and cytoglobin were evaluated.

Results: Arundic acid (300 μM) inhibited the activation of primary rat stellate cells, as determined by morphological transformation and α-smooth muscle actin expression, after both prophylactic and therapeutic treatment. The level of α-smooth muscle actin mRNA showed a dose-dependent decrease in response to arundic acid, and 50 μM arundic acid exhibited the maximum inhibition of collagen 1α1 mRNA expression. In contrast, arundic acid triggered an unexpected increase in mRNA and protein levels of cytoglobin, the fourth globin in mammals expressed exclusively in hepatic stellate cells. The effect of arundic acid on the level of α-smooth muscle actin mRNA was abrogated in HSCs treated with cytoglobin siRNA. Arundic acid decreased the expression of collagen 1α1 mRNA in LX-2 cells.

Conclusion: Arundic acid affects the activation process of hepatic stellate cells via the unexpected induction of cytoglobin.