Relationship Between TGF-?₁ Expression In Pulmonary Vessels And Cigarette Smoke-induced Rat Pulmonary Vascular Remodeling

Objective: To investigate the variations of transforming growth factor-beta 1(TGF-?1) expression in pulmonary vasculature of rats exposed to cigarette smoke and its roles in pulmonary vascular remodeling.Methods: Sixty SD rats were randomly assigned into control group and smoke exposure group; the latter was further divided into four time point of 2,4,8,12 weeks. Hematoxylin-Eosin(HE) staining was performed to observe the pulmonary artery wall thickness(WT%), and percentage of muscularized arteries was determined by antialpha-smooth muscle actin(?-SMA)antibody staining. Immunohistochemistry methods were performed to determine proliferating cell nuclear antigen(PCNA)?TGF-?1 protein expression in pulmonary artery smooth muscle. The expression of TGF-?1 m RNA in pulmonary arteries were evaluated by real-time quantification PCR(RT-PCR).Results:(1) Compared to control group, Pulmonary vessel wall thickness and percentage of muscularized vessels were significantly increased in S-2W, S-4W, S-8W and S-12 W group(all P<0.05).(2) Significantly increases of PCNA and TGF-?1 protein expressions in smoke exposure groups were observed compared to control group. There were markedly differences between five groups(all P<0.05).(3) Compared to control group, TGF-?1 m RNA expression in pulmonary artery walls obviously increased. There were significant differences between S-4W, S-8W and S-12 W group(all P<0.05).(4) Expressions of TGF-?1 m RNA and protein were positively correlated with the severity ofpulmonary vascular muscularization and WT%(all P<0.01), and both TGF-?1 m RNA and protein were positively correlate with PCNA(all P<0.01).Conclusion: 1.Pulmonary artery remodeling could happen in early period after smoke exposure, and became worse with prolonged smoke exposure. 2. TGF-?1 expression in pulmonary arteries in smoke groups obviously increased,which suggested that TGF-?1 might be associated with pulmonary artery remodeling induced by cigarette smoke. 3. Cigarette smoke exposure might up-regulate TGF-?1 expression in pulmonary vessels and directly lead to pulmonary vascular remodeling in rats via regulating pulmonary artery smooth muscle cells(PASMCs) proliferation.