Baicalin attenuates transforming growth factor-β1-induced human pulmonary artery smooth muscle cell proliferation and phenotypic switch by inhibiting hypoxia inducible factor-1α and aryl hydrocarbon receptor expression.

OBJECTIVES

Baicalin, a natural flavone, has antithrombotic, antihyperlipidemic and antiinflammortory activity. It can also inhibit cancer cell proliferation and reduce brain cell apoptosis. This study aimed to elucidate the effect of baicalin on the excessive proliferation of human pulmonary arterial smooth muscle cells (HPASMCs) induced by transforming growth factor-β1 (TGF-β1) and to investigate the roles of hypoxia inducible factor-1α (HIF-1α) and aryl hydrocarbon receptor (AhR) in mediating this TGF-β1-induced excessive proliferation of HPASMCs.

METHODS

TGF-β1-induced proliferation of HPASMCs was assayed using the CCK8 method. The cellular phenotype was identified by immunocytochemical staining. Expression of HIF-1α and AhR mRNA was determined by real-time quantitative PCR.

KEY FINDINGS: TGF-β1 promoted significantly HPASMC proliferation (P < 0.05) and induced a phenotypic switch from the contractile to synthetic type. Baicalin inhibited this TGF-β1-induced phenotypic switch and consequently the excessive growth of HPASMCs in a time-dependent and dose-dependent manner (P < 0.05). Furthermore, baicalin attenuated the abnormal proliferation of HPASMCs through suppression of the HIF-1α and AhR pathways.

CONCLUSIONS

Our study shows that baicalin has the potential to be used as a novel drug in the treatment of pulmonary arterial hypertension pathology by antagonizing HIF-1α and AhR expression and subsequently decreasing HPASMC proliferation and the phenotypic switch.