Effects Of HMGB1 On The Proliferation, Migration And Apoptosis Of Hpasmcs In Vitro

Objective:To investigate the effects of high mobility group box protein 1 (HMGB1) on the proliferation, migration and apoptosis of human pulmonary artery smooth muscle cells (HPASMC) in vitro.Methods:We cultivated the HPASMC for 5th to 8th generations, and then began the following experiments. The HPASMC were devided into five different groups according to various concentrations of HMGB1:Ong/ml,1 ng/ml,10 ng/ml, 100 ng/ml and 1000 ng/ml. After 24h or 48h, cell proliferation was determined by indirect cell counting with methyl thiazol tetrazolium staining. We used modified Boyden chambers to count the amount of migratory cells to detect the effects of HMGB1 on the migration of HPASMC. We detected the effects of HMGB1 on the apoptosis of HPASMC by the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) technique.Results:(1) The quantites of cells of HMGB1 groups after 24 hours and 48 hours were increased, comparing to the negative control group (P＜0.01). HMGB1 induced proliferation of HPASMC in a concentration-dependent manner, starting at doses as low as 1 ng/ml and coming up to a platform response at 100 ng/ml. (2) Compared to control group, HMGB1 promoted HPASMC traveling through the polycarbonate filters with 8μm pores (P<0.01). HMGB1 stimulated migration of HPASMC in a concentration-dependent manner, starting at doses as low as 1 ng/ml and with a 2.33-fold maximal response at 100 ng/ml. (3)The rate of TUNEL positive cells dealed with Ong/ml,1 ng/ml,10 ng/ml,100 ng/ml and 1000 ng/ml HMGB1 for 48 hours was 8.56%,8.22%,7.61%,7.50%,7.11%(P>0.05) respectively.Conclusion:1. HMGB1 could induce proliferation and migration of HPASMC in a concentration-dependent manner, and come up to peak response at the concentration of 100ng/ml.2. HMGB1 could not influence the apoptosis of HPASMC.3.HMGB1 promote pulmonary vascular remodeling by induce proliferation and migration of HPASMC.