Regulatory effects of HIF-1α and HO-1 in hypoxia-induced proliferation of pulmonary arterial smooth muscle cells in yak

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and heme oxygenase-1 (HO-1) are important transcription regulators in hypoxic cells and for maintaining cellular homeostasis, but it is unclear whether they participate in hypoxiainduced excessive proliferation of yak pulmonary artery smooth muscle cells (PASMCs). In this study, we identified distribution of HIF-1 alpha and HO-1 in yak lungs. Immunohistochemistry and immunofluorescence results revealed that both HIF-1 alpha and HO-1 were mainly concentrated in the medial layer of small pulmonary arteries. Furthermore, under induced-hypoxic conditions, we investigated HIF-1 alpha and HO-1 protein expression and studied their potential involvement in yak PASMCs proliferation and apoptosis. Western blot results also showed that both factors significantly increased in age-dependent manner and upregulated in hypoxic PASMCs (which exhibited obvious proliferation and anti-apoptosis phenomena). HIF-1 alpha up-regulation by DMOG increased the proliferation and anti-apoptosis of PASMCs, while HIF-1 alpha down-regulation by LW6 decreased proliferation and promoted apoptosis. More so, treatment with ZnPP under hypoxic conditions down-regulated HO-1 expression, stimulated proliferation, and resisted apoptosis in yak PASMCs. Taken together, our study demonstrated that both HIF-1 alpha and HO-1 participated in PASMCs proliferation and apoptosis, suggesting that HO-1 is important for inhibition of yak PASMCs proliferation while HIF-1 alpha promoted hypoxia-induced yak PASMCs proliferation.

Automated summary

This study demonstrated that both HIF-1 alpha and HO-1 are involved in the proliferation and apoptosis of PASMCs, with HO-1 playing a crucial role in inhibiting yak PASMCs proliferation, while HIF-1 alpha promoting hypoxia-induced yak PASMCs proliferation.