Effect of retinoid kappa receptor alpha (RXRalpha) transfection on the proliferation and phenotype of rat hepatic stellate cells in vitro.

Objective To study the effect of retinoid X receptor alpha (RXRa) transfection plus treatment with the RXRa ligand, 9-cis-RA, on the proliferation and phenotype of platelet-derived growth factor (PDGF)-activated hepatic stellate cells (HSCs). Methods PDGF activated rat hepatic stellate cells were transfected with eukaryotic expression vector pcDNA3.1- human RXRa, and confirmed by Western blot. Proliferation of transfected HSC was assayed by bromodeoxyuridine (BrdU) incorporation as well as MTT, and the phenotype (a-smooth muscle actin, desmin) was observed by immunocytochemistry with image analysis. Results Transfection of the RXRa gene and treatment with ligand 9-cis-RA of PDGF-activated HSCs extended the increased expression of RXRa protein for at least 168 hours. Cell proliferation and expressions of alpha-smooth muscle actin (a-SMA) and desmin were blocked, compared with groups of sham-transfected, PDGF-activated, no transfection, no ligand treatment, and irrelevant ligand treated HSCs. Conclusion Transfection with the RXRa gene followed by 9-cis-RA ligand treatment will inhibit the proliferation and reverse the phenotype of activated HSC.