Fibroblast Growth Factor 9 Inhibits PDGF-BB-Induced Phenotypic Phenotype Switch of Pulmonary Vascular Smooth Muscle Cells
ZHENG Yan, PENG Linqian, DONG Yongjie, HUANG Wei*
The purpose of this study is to investigate the role of FGF9 (fibroblast growth factor 9) in PAH (pulmonary arterial hypertension) and phenotype switch of pulmonary vascular smooth muscle cells. Rat model of pulmonary arterial hypertension was induced by MCT (monocrotaline), and the expression of FGF9 in lung tissue was detected by Western blot. PDGF-BB (platelet-derived growth factor-BB) induced phenotype switch of PASMCs (pulmonary artery smooth muscle cells) and then Western blot was used to detect the expression of FGF9. Exogenous rhFGF9 (recombinant human fibroblast growth factor 9) interfered with PASMCs. Then scratch assay and Western blot were used to measure cell migration, the expression of phenotype-related proteins [α-SMA (α-smooth muscle actin), OPN (osteopontin)], PCNA (proliferating cell nuclear antigen) and PDGFR-β (plateletderived growth factor receptor β), respectively. After knock-down of FGF9 by siRNA, Western blot was used to analyze the expression of phenotypic markers and PCNA of PASMCs. The results showed that the expression of FGF9 in the lung tissue and PSMCs of rats were significantly reduced (P<0.05). The expression of PDGFR-β and α-SMA (contractile phenotype marker) was down-regulated (P<0.05), while the protein levels of PCNA and OPN (synthetic phenotypic marker) were increased in PASMCs treated with PDGF-BB (P<0.05), and migration of PASMCs induced by PDGF-BB. The changes in cell migration and expression of α-SMA and OPN were blocked by rhFGF9, while rhFGF9 did not affect the expression of PDGFR-β and PCNA. Knock-down of FGF9 reduced the expression of α-SMA without affecting the expression of PCNA and OPN, which suggested that FGF9 was related to the contractile phenotype of PASMCs. In summary, rhFGF9 represses the phenotype switch and migration of PASMCs induced by PDGF-BB, and the contractile phenotype of PASMCs was regulated by silencing FGF9. Therefore, FGF9 may participate in the pathogenesis of PAH.
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