OBJECTIVETo study the effect of retinoid kappa receptor alpha (RXRalpha) transfection plus treatment with the RXRalpha ligand, 9-cis-RA, on the proliferation and phenotype of platelet-derived growth factor (PDGF) activated hepatic stellate cells (HSCs).

METHODSPDGF activated rat hepatic stellate cells were transfected with eukaryotic expression vector pcDNA3.1- human RXRalpha, and confirmed by Western blot. Proliferation of transfected HSC was assayed by bromodeoxyuridine (BrdU) incorporation as well as MTT, and the phenotype (alpha-smooth muscle actin, desmin) was observed by immunocytochemistry with image analysis.

RESULTSTransfection of the RXRalpha gene and treatment with ligand 9-cis-RA of PDGF-activated HSCs extended the increased expression of RXRalpha protein for at least 168 hours. Cell proliferation and expressions of alpha- smooth muscle actin (alpha-SMA) and desmin were blocked, compared with groups of sham-transfected, PDGF-activated, no transfection, no ligand treatment, and irrelevant ligand treated HSCs.

CONCLUSIONTransfection with the RXRalpha gene followed by 9-cis-RA ligand treatment will inhibit the proliferation and reverse the phenotype of activated HSC.

Animals ; Cell Division ; Cells, Cultured ; Liver ; cytology ; Liver Cirrhosis ; etiology ; Male ; Phenotype ; Platelet-Derived Growth Factor ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Retinoic Acid ; genetics ; physiology ; Retinoid X Receptors ; Transcription Factors ; genetics ; physiology ; Transfection