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

• Published in: Acta biochimica et biophysica Sinica Vol. 39; no. 1; pp. 73 - 80
• Main Authors: JIANG, Yongliang, DAI, Aiguo, LI, Qifang, HU, Ruicheng
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2007
• Subjects: hypertension; hypoxia; hypoxia inducible factor‐1α; lung; transforming growth factor‐β1
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1111/j.1745-7270.2007.00249.x

The present study was undertaken to investigate the dynamic expression of hypoxia inducible factor‐1β (HIF‐1β) and transforming growth factor‐β 1 (TGF‐β 1) 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 decreasing after 14 and 21 d of hypoxia. Linear correlation analysis showed that HIF‐1α mRNA, TGF‐β1 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. Edited by Minghua XU