Rat hepatic stellate cells acquire retinoid responsiveness after activation in vitro by post-transcriptional regulation of retinoic acid receptor alpha gene expression

Abstract

Activation of hepatic stellate cells (HSCs) is a key process in liver fibrogenesis and retinoid loss is a remarkable feature of activated HSCs. However, roles of retinoids in liver fibrogenesis are obscure. We show that mRNA levels of RARα, β and γ were decreased during rat HSC activation in vitro. However, protein levels of RARα and β were increased during HSC activation. A retinoic acid response element-containing luciferase assay indicated that HSCs became responsive to retinoids only after activation in vitro and that this response was mediated by, at least in part, RARα subtype. Immunocytochemical analysis showed that RARα proteins were mainly distributed in cytosol as many spots. All- trans retinoic acid treatment strongly lowered the cytosolic RARα protein levels. These results indicate that rat HSCs become retinoid responsive after activation in vitro, through post-transcriptional up-regulation of RARα gene expression.