[Effects of all-trans retinoic acid on phenotype switch and migration of human pulmonary artery smooth muscle cells in vitro and the possible mechanisms].

OBJECTIVE: To investigate the effects of all-trans retinoic acid (atRA) on phenotype switch and migration of human pulmonary artery smooth muscle cells (PASMC) in vitro and the possible mechanisms. METHODS: Cultured human PASMC were divided into 8 groups randomly: group A (control group), group B (vehicle group), group C (treated with 10% fetal cattle serum), group D, group E, group F, group G, and group H (treated with atRA at the concentrations of 0.001 micromol/L, 0.01 micromol/L, 0.1 micromol/L, 1 micromol/L, 10 micromol/L respectively as well as 10% fetal cattle serum). Then, expression of JWA mRNA in human PASMC was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), cell migration was measured using modified Boyden's chamber, and expression of SM-alpha-actin mRNA and protein was detected by RT-PCR and immunohistochemistry respectively. The difference between the groups was analyzed. RESULTS: There was no significant difference in the JWA mRNA expression of human PASMC between group A (0.125 +/- 0.014), group B (0.164 +/- 0.018) and group C (0.164 +/- 0.006), but the JWA mRNA expression in group D (0.326 +/- 0.018), group E (0.440 +/- 0.033), group F (0.460 +/- 0.040), group G (0.589 +/- 0.024) and group H (0.821 +/- 0.050) were significantly higher than those of group A, group B and group C (all P < 0.01). The number of migrating cells in group C (30.4 +/- 7.4) was higher than those in group A (7.2 +/- 1.9) and group B (6.8 +/- 2.3, all P < 0.01), but the number of migrating cells in group D (21.8 +/- 2.9), group E (17.2 +/- 2.3), group F (14.4 +/- 3.5), group G (12.6 +/- 3.4) and group H (8.8 +/- 2.4) was significantly lower than that in group C (all P < 0.01), and there was no significant difference between group G, group H and group A, group B. The SM-alpha-actin protein expression in group C (0.219 +/- 0.018) was significantly lower than those in group A (0.319 +/- 0.011) and group B (0.325 +/- 0.005, all P < 0.01), but the protein expression in group E (0.328 +/- 0.016), group F (0.386 +/- 0.025), group G (0.442 +/- 0.017) and group H (0.501 +/- 0.018) was significantly higher than that in group C (all P < 0.01), while that in group F, group G and group H was significantly higher than those in group A and group B (all P < 0.01). The SM-alpha-actin mRNA expression in group C (0.144 +/- 0.009) was significantly lower than those in group A (0.299 +/- 0.023) and group B (0.296 +/- 0.041, all P < 0.01), but the mRNA expression in group D (0.487 +/- 0.014), group E (0.501 +/- 0.020), group F (0.611 +/- 0.018), group G (0.774 +/- 0.013) and group H (0.851 +/- 0.026) was significantly higher than those in group A, group B and group C (all P < 0.01). CONCLUSION: atRA increased JWA gene expression in human pulmonary artery smooth muscle cells, and meanwhile, the cells differentiated into a contractive phenotype and the cell migration decreased.