Hypoxia-inducible factor (HIF)-α subunits (HIF-1α,HIF-2α and HIF-3α),which play a pivotalrole during the development of hypoxia-induced pulmonary hypertension (HPH),are regulated through post-U’anslational hydroxylation by their three prolyl hydroxylase domain-containing proteins (PHD 1,PHD2 and PHD3).PHDs could also be regulated by HIF.But differential and reciprocal regulation between HIF-α and PHDs duringthe development of HPH remains unclear.To investigate this problem,a rat HPH model was established.Meanpulmonary arterial pressure increased significantly after 7 d of hypoxia.Pulmonary artery remodeling indexand right ventricular hypertrophy became evident after 14 d of hypoxia.HIF-1α and HIF-2α mRNA increasedslightly after 7 d of hypoxia,but HIF-3α increased significantly after 3 d of hypoxia.The protein expressionlevels of all three HIF-α were markedly upregulated after exposure to hypoxia.PHD2 mRNA and proteinexpression levels were upregulated after 3 d of hypoxia;PHD 1 protein declined after 14 d of hypoxia withoutsignificant mRNA changes.PHD3 mRNA and protein were markedly upregulated after 3 d of hypoxia,then themRNA remained at a high level,but the protein declined after 14 d of hypoxia.In hypoxic animals,HIF-lotproteins negatively correlated with PHD2 proteins,whereas HIF-2α and HIF-3α proteins showed negativecorrelations with PHD3 and PHD 1 proteins,respectively.All three HIF-α proteins were positively correlatedwith PHD2 and PHD3 mRNA.In the present study,HIF-α subunits and PHDs showed differential andreciprocal regulation,and this might play a key pathogenesis role in hypoxia-induced pulmonary hypertension. Hypoxia-inducible factor (HIF) -α subunits (HIF-1α, HIF-2α and HIF-3α), which play a pivotal role in the development of hypoxia-induced pulmonary hypertension (HPH), are regulated through post-U’lationlation hydroxylation by their three prolyl hydroxylase domain-containing proteins (PHD 1, PHD2 and PHD3). PHDs could also be regulated by HIF.But differential and reciprocal regulation between HIF-α and PHDs during the development of HPH remains unclear. To investigate this problem, a rat HPH model was established. Manpulmonary 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-1α and HIF-2α mRNA increased significantly after 7 d of hypoxia, but HIF- 3α increased significantly after 3 days of hypoxia. The protein expression levels of all three HIF-α were markedly upregulated after exposure to hypoxia. PHD2 mRNA and proteinexpression levels were upregulated after 3 days of hypoxia; PHD 1 protein declined after 14 d of hypoxia withoutsignificant mRNA changes. PHD3 mRNA and protein were markedly upregulated after 3 d of hypoxia, then theRNA remained at a high level, but the protein declined after 14 d of hypoxia. In hypoxic animals, HIF-lotproteins negatively correlated with PHD2 proteins, whereas HIF-2α and HIF-3α proteins showed negativecorrelations with PHD3 and PHD1 proteins, respectively. All three HIF-α proteins were positively associated with PHD2 and PHD3 mRNA. In the present study, HIF-α subunits and PHDs showed differential andreciprocal regulation, and this might play a key pathogenesis role in hypoxia-induced pulmonary hypertension.