Changes of TGF-β1 and CTGF in rats with increased blood flow-induced pulmonary artery hypertension

Abstract

To evaluate the role of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in the pathogenesis of pulmonary artery hypertension, we observed the dynamic expression of TGF-β1 and CTGF in rats with high blood flow. Fifty adult male SD rats were randomly divided into 5 groups: a sham group (group S) and groups with right pneumonectomy for 1, 2, 4 and 6 weeks (PE1, PE2, PE4 and PE6 group), 10 rats per group. The mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were measured. TGF-β1 and CTGF protein expression in the lung tissues were determined with immunohistochemistry and Western blot. The expression of TGF-β1 mRNA and CTGF mRNA in the lung tissues was evaluated by RT-PCR. Compared with group S, the mPAP and RVHI in the rats were significantly increased in group PE1, PE2, PE4, and PE6 (P<0.05); the indicators of vascular remodeling [(MA+PMA)%, RMT, and RMA] were markedly elevated in group PE4 and PE6 (P<0.05), but not in group PE1 and PE2. Immunohistochemical staining of TGF-β1 and CTGF were more prominent in all of the right pneumonectomy groups than in the sham group. Western blot showed that the level of TGF-β1 protein was significantly increased in all of the right pneumonectomy groups (P<0.01), and the peak was observed in group PE2, whereas the level of CTGF protein was markedly elevated in group PE4 and PE6 (P<0.05), but no change was noticed in group PE1 and PE2. Compare to group S, the mRNA level of TGF-β1 was dramatically increased in all right pneumonectomy groups (P<0.01), peaked at group PE2, and remained high in group PE4 and PE6. In contrast, the elevation of mRNA level of CTGF was not significant in group PE1, but group PE2, PE4 and PE6 demonstrated significant mRNA level of CTGF (P<0.01). Correlation analysis showed that the protein and mRNA levels of CTGF were positively correlated with RMT and RMA ( r=0.743, r=0.906; P<0.05), while no correlation between the protein and mRNA level of TGF-β1 with RMT or RMA. There was no correlation between the mRNA level of TGF-β1 and CTGF. TGF-β1 and CTGF play a role in the pathogenesis of increased pulmonary blood flow-induced pulmonary hypertension.