2. Academic Validation
  3. Regulatory effects of HIF-1α and HO-1 in hypoxia-induced proliferation of pulmonary arterial smooth muscle cells in yak

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

  • Cell Signal. 2021 Nov;87:110140. doi: 10.1016/j.cellsig.2021.110140.
Huizhu Zhang 1,  Honghong He 2,  Yan Cui 3,  Sijiu Yu 4,  Shijie Li 1,  Seth Yaw Afedo 1,  Yali Wang 1,  Xuefeng Bai 1,  Junfeng He 1
Affiliations

Affiliations

  • 1 Laboratory of Animal Anatomy & Tissue Embryology, Department of Basic Veterinary Medicine, Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
  • 2 Gansu Province Livestock Embryo Engineering Research Center, Department of Clinical Veterinary Medicine, Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
  • 3 Laboratory of Animal Anatomy & Tissue Embryology, Department of Basic Veterinary Medicine, Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; Gansu Province Livestock Embryo Engineering Research Center, Department of Clinical Veterinary Medicine, Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China. Electronic address: cuiyan@gsau.edu.cn.
  • 4 Laboratory of Animal Anatomy & Tissue Embryology, Department of Basic Veterinary Medicine, Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; Gansu Province Livestock Embryo Engineering Research Center, Department of Clinical Veterinary Medicine, Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
PMID: 34478827 DOI: 10.1016/j.cellsig.2021.110140
Abstract

Hypoxia-inducible factor-1α (HIF-1α) 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 hypoxia-induced excessive proliferation of yak pulmonary artery smooth muscle cells (PASMCs). In this study, we identified distribution of HIF-1α and HO-1 in yak lungs. Immunohistochemistry and immunofluorescence results revealed that both HIF-1α and HO-1 were mainly concentrated in the medial layer of small pulmonary arteries. Furthermore, under induced-hypoxic conditions, we investigated HIF-1α 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-1α up-regulation by DMOG increased the proliferation and anti-apoptosis of PASMCs, while HIF-1α 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-1α and HO-1 participated in PASMCs proliferation and Apoptosis, suggesting that HO-1 is important for inhibition of yak PASMCs proliferation while HIF-1α promoted hypoxia-induced yak PASMCs proliferation.

Keywords

Apoptosis; HIF-1α; HO-1; Hypoxia; PASMCs proliferation; Yak.

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