Study on the Regulatory Mechanism of the PDK1-Mediated TGF-β/Smad Signaling Pathway in Hypoxia-Induced Yak Lungs
Author:
Zhang Yiyang1234, Wang Jun4, Zhang Meng4, Li Xiaoyun1234, Zhang Fan1234, Zhou Manlin1234, Yang Kun1234, Chen Weiji4, Ding Haie4, Tan Xiao4, Zhang Qian5, Qiao Zilin1234
Affiliation:
1. Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Northwest Minzu University, Lanzhou 730030, China 2. Gansu Tech Innovation Center of Animal Cell, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China 3. Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China 4. Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China 5. College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
Abstract
The aim of this study was to investigate the effects of hypoxia-induced phenotype, glucose metabolism, ROS levels, and the PDK1-mediated regulation of TGF-β/Smad signaling in yellow cattles, yaks, and those overexpressing PDK1 PASMCs using growth curves, flow cytometry, scratch experiments, glucose and lactic acid assays, RT-qPCR, and Western blotting. The results showed that hypoxia significantly promoted proliferation, migration, antiapoptosis, ROS levels, glucose consumption, and lactate production in yellow cattle PASMCs (p < 0.05), and the cells were dedifferentiated from the contractile phenotype; conversely, hypoxia had no significant effect on yak PASMCs (p > 0.05). PDK1 overexpression significantly promoted proliferation, antiapoptosis, glucose consumption, and lactate production in yak PASMCs under normoxia and hypoxia (p < 0.05), decreased their migration levels under hypoxia (p < 0.05), and dedifferentiated the contractile phenotype of the cells. Overexpression of PDK1 in yak PASMCs is detrimental to their adaptation to hypoxic environments. Yak PASMCs adapted to the effects of hypoxia on lung tissue by downregulating the expression of genes related to the PDK1 and TGF-β/Smad signaling pathways. Taken together, the regulation of PDK1-mediated TGF-β/Smad signaling may be involved in the process of yaks’ adaptation to the hypoxic environment of the plateau, reflecting the good adaptive ability of yaks. The present study provides basic information to further elucidate the mechanism of PDK1-mediated TGF-β/Smad signaling induced by hypoxia in the lungs of yaks, as well as target genes for the treatment of plateau diseases in humans and animals.
Funder
National Natural Science Foundation of China Natural Science Foundation of Gansu Province Gansu Province Education Science and Technology Innovation Programme Lanzhou Youth Science and Technology Talent Innovation Program Fundamental Research Funds for the Central Universities
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