Glyburide prevents pulmonary artery smooth muscle cell proliferation and migration via inhibiting NLRP3 activation

Abstract

Objective: To investigate whether glyburide prevents platelet-derived growth factor (PDGF) induced pulmonary artery smooth muscle cells(PASMCs) proliferation and migration via inhibiting nucleotide binding domain leucine-rich repeat-containing receptors protein 3(NLRP3) inflammasome activation. Methods: PASMCs were divided into 4 groups: control group, glyburide group, PDGF group and PDGF+ glyburide group. Cell proliferation and migration were assessed by MTT and Transwell respectively. The NLRP3 inflammasome activation was assessed by Western blot. Results: Compared with the control group, the protein expressions of NLRP3, caspase-1 and IL-1β in PASMCs were increased to (1.38±0.09, t=3.998, P<0.001), (1.32±0.1, t=3.268, P<0.01)and(1.43±0.19) (t=2.096, P<0.05) folds in the PDGF group. Glyburide had no effect on NLRP3, caspase-1 and IL-1β expression as compared with the control group, while the NLRP3, caspase-1 and IL-1β were decreased by(20.49±7.6)% (t=2.862, P<0.01), (32.94±3.44)% (t=4.154, P<0.001) and (24.67±5.29)% (t=2.335, P<0.05) in the PDGF+ glyburide group, respectively, as compared with the PDGF group. Compared with the control group, the PASMCs proliferation and migration in the PDGF group were significantly increased to (1.74±0.23, t=4.717, P<0.001) and (3.12±0.8, t=5.249, P<0.001) folds, respectively. Compared with the control group, glyburide had no effect on PASMCs proliferation and migration. In PDGF+ glyburide group, cell proliferation was reduced by (50.5±4.27)% (t=4.462, P<0.001) and cell migration count was lower than in the PDGF group (42.77±2.84)% (t=3.716, P<0.001). Conclusion: Glyburide could ameliorate PDGF-induced PASMCs proliferation and migration by inhibiting NLRP3 inflammasome activation.