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Differential and reciprocal regulation between hypoxia-inducible factor-alpha subunits and their prolyl hydroxylases in pulmonary arteries of rat with hypoxia-induced hypertension.

Authors: Chen, YR  Dai, AG  Hu, RC  Jiang, YL 
Citation: Chen YR, etal., Acta Biochim Biophys Sin (Shanghai). 2006 Jun;38(6):423-34.
Pubmed: (View Article at PubMed) PMID:16761101

Hypoxia-inducible factor (HIF)-alpha subunits (HIF-1alpha, HIF-2alpha and HIF-3alpha), which play a pivotal role during the development of hypoxia-induced pulmonary hypertension (HPH), are regulated through post-translational hydroxylation by their three prolyl hydroxylase domain-containing proteins (PHD1, PHD2 and PHD3). PHDs could also be regulated by HIF. But differential and reciprocal regulation between HIF-alpha and PHDs during the development of HPH remains unclear. To investigate this problem, a rat HPH model was established. Mean pulmonary arterial pressure increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. HIF-1alpha and HIF-2alpha mRNA increased slightly after 7 d of hypoxia, but HIF-3alpha increased significantly after 3 d of hypoxia. The protein expression levels of all three HIF-alpha were markedly upregulated after exposure to hypoxia. PHD2 mRNA and protein expression levels were upregulated after 3 d of hypoxia; PHD1 protein declined after 14 d of hypoxia without significant mRNA changes. PHD3 mRNA and protein were markedly upregulated after 3 d of hypoxia, then the mRNA remained at a high level, but the protein declined after 14 d of hypoxia. In hypoxic animals, HIF-1alpha proteins negatively correlated with PHD2 proteins, whereas HIF-2alpha and HIF-3alpha proteins showed negative correlations with PHD3 and PHD1 proteins, respectively. All three HIF-alpha proteins were positively correlated with PHD2 and PHD3 mRNA. In the present study, HIF-alpha subunits and PHDs showed differential and reciprocal regulation, and this might play a key pathogenesis role in hypoxia-induced pulmonary hypertension.

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CRRD Object Information
CRRD ID: 11252085
Created: 2016-06-23
Species: All species
Last Modified: 2016-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.