Study on the Regulatory Mechanism of the PDK1-Mediated TGF-β/Smad Signaling Pathway in Hypoxia-Induced Yak Lungs
Yiyang Zhang,
Jun Wang,
Meng Zhang,
Xiaoyun Li,
Fan Zhang,
Manlin Zhou,
Kun Yang,
Weiji Chen,
Haie Ding,
Xiao Tan,
Qian Zhang,
Zilin Qiao
Affiliations
Yiyang Zhang
Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Northwest Minzu University, Lanzhou 730030, China
Jun Wang
Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China
Meng Zhang
Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China
Xiaoyun Li
Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Northwest Minzu University, Lanzhou 730030, China
Fan Zhang
Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Northwest Minzu University, Lanzhou 730030, China
Manlin Zhou
Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Northwest Minzu University, Lanzhou 730030, China
Kun Yang
Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Northwest Minzu University, Lanzhou 730030, China
Weiji Chen
Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China
Haie Ding
Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China
Xiao Tan
Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China
Qian Zhang
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
Zilin Qiao
Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Northwest Minzu University, Lanzhou 730030, China
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 p > 0.05). PDK1 overexpression significantly promoted proliferation, antiapoptosis, glucose consumption, and lactate production in yak PASMCs under normoxia and hypoxia (p 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.
