Hypoxia Induces Transforming Growth Factor-β1 Gene Expression in the Pulmonary Artery of Rats via Hypoxia-inducible Factor-1α  

作　　者：Yongliang JIANG Aiguo DAI Qifang LI and Ruicheng HU Depoptment of Respiratory Medicine,Hunan Institute of Gerontology,Hunan Province Geriatric Hospital,Changsha 410001,China 

出　　处：《Acta Biochimica et Biophysica Sinica》2007年第1期73-80,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China （No. 30270581）; the Major Science and Technology Foundation of the Ministry of Education of China （No. 03091） ;the Natural Science Foundation of Hunan Province （No. 05JJ30073）

摘　　要：The present study was undertaken to investigate the dynamic expression of hypoxia inducible factor-1α （HIF-1α） and transforming growth factor-β1 （TGF-β1） in hypoxia-induced pulmonary hypertension of rats. It was found that mean pulmonary arterial pressure （mPAP） increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. HIF-1α mRNA staining was less positive in the control, hypoxia for 3 d and hypoxia for 7 d, but began to enhance significantly after 14 d of hypoxia, then remained stable. Expression of HIF-1α protein in the control was less positive, but was up-regulated in pulmonary arterial tunica intima of all hypoxic rats. TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-β1 protein staining was less positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia, and then weakening after 14 and 21 d of hypoxia. Western blotting showed that HIF-1α protein levels increased significantly after 7 d of hypoxia and then remained at a high level. TGF-β1 protein level was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia, and then decreasingafter 14 and 21 d of hypoxia. Linear correlation analysis showed that HIF-1α mRNA, TGF-1α mRNA, TGF-β1 protein were positively correlated with mPAP, vessel morphometry and right ventricular hypertrophy index. TGF-β1 protein （tunica adventitia） was negatively correlated with HIF-1α mRNA. Taken together, our results suggest that changes in HIF-1α and TGF-β1 expression after hypoxia play an important role in hypoxia-induced pulmonary hypertension of rats.The present study was undertaken to investigate the dynamic expression of hypoxia inducible factor-1α （HIF-1α） and transforming growth factor-β1 （TGF-β1） in hypoxia-induced pulmonary hypertension of rats. It was found that mean pulmonary arterial pressure （mPAP） increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. HIF-1α mRNA staining was less positive in the control, hypoxia for 3 d and hypoxia for 7 d, but began to enhance significantly after 14 d of hypoxia, then remained stable. Expression of HIF-1α protein in the control was less positive, but was up-regulated in pulmonary arterial tunica intima of all hypoxic rats. TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-β1 protein staining was less positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia, and then weakening after 14 and 21 d of hypoxia. Western blotting showed that HIF-1α protein levels increased significantly after 7 d of hypoxia and then remained at a high level. TGF-β1 protein level was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia, and then decreasingafter 14 and 21 d of hypoxia. Linear correlation analysis showed that HIF-1α mRNA, TGF-1α mRNA, TGF-β1 protein were positively correlated with mPAP, vessel morphometry and right ventricular hypertrophy index. TGF-β1 protein （tunica adventitia） was negatively correlated with HIF-1α mRNA. Taken together, our results suggest that changes in HIF-1α and TGF-β1 expression after hypoxia play an important role in hypoxia-induced pulmonary hypertension of rats.

关 键 词：hypoxia inducible factor-1α transforming growth factor-β1 HYPERTENSION LUNG HYPOXIA 

分 类 号：R543[医药卫生—心血管疾病]