Role of connective tissue growth factor-integrin β1 signal pathway in the proliferation and migration of pulmonary arterial smooth muscle cell

Abstract

Objective To explore the mechanisms of integrin β1 on connective tissue growth factor(CTGF) -induced proliferation, migration, change of cytoskeleton of pulmonary arterial smooth muscle cell(PASMC) in vitro, and to investigate the effects of CTGF-integrin β1 signal pathway on pulmonary vascular remodeling in pulmonary arterial hypertension(PAH). Methods Pulmonary artery smooth muscle cells of SD rats were cultured in vitro.WST-1 assay was used to detect the effects of anti-integrin β1 antibody on CTGF-induced proliferation of PASMC.Transwell chambers were used to observe the effects of anti-integrin β1 antibody on CTGF-induced migration of PASMC.The cytoskeletal rearrangement was observed with coomassie brilliant blue R250 staining and Confocal Lasar Scanning Microscopy(CLSM). Results Different concentration of anti-integrin β1 antibody could inhibit the proliferation of PASMC induced by CTGF, which presents concentration dependent pattern(P<0.05). The higher the concentration of anti-integrin β1 antibody, the more severity the proliferation of PASMC induced by CTGF was inhibited.and inhibition rate of PASMC proliferation was the highest at 72 hours.Anti-integrin β1 antibody(15 mg/L) decreased significantly the number of PASMC passing through Transwell induced by CTGF, compared with CTGF group(P<0.01). Meanwhile, anti-integrin β1 antibody could change cytoskeletal rearrangement of PASMC induced by CTGF. Conclusions Integrin β1 mediates the proliferation, migration, cytoskeletal rearrangement of PASMC induced by CTGF.The CTGF-integrin β1 signal pathway may play a key role in proliferation, migration, cytoskeletal rearrangement PASMC. Key words: Integrin; Connective tissue growth factoial; Pulmonary arterial smooth muscle cell; Proliferation; Migration