Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors

SIMPLE SUMMARY: The lung is a key organ that exhibits adaptive changes in response to high altitude in mammals. The prolonged presence of lowland cattle at high altitude leads to the abnormal proliferation of pulmonary vascular smooth muscle cells, resulting in pulmonary vascular remodeling, whereas the underlying molecular mechanisms in yaks, a representative model for mammalian high-altitude acclimatization studies, remain unknown. In this manuscript, we investigated the transcriptomic analysis of yak and cattle pulmonary artery smooth muscle cells in vitro at different oxygen concentrations (1%, 10%, and 20%) and in vivo to observe the lung tissue structure as well as the distribution of PDK1, HIF-1α, and VEGF and differences in their expression in the lungs of plateau yaks and plains cattle. The results showed that the HIF-1 signaling pathway, glucose metabolism pathway, and related factors (HK2/PGK1/ALDOA/ALDH1A3/EHHADH) were closely related to each other, that there were obvious differences between yak lung tissues and those of plains cattle, and that there might be a regulatory relationship between the differences in the distribution and expression of PDK1, HIF-1α, and VEGF and the adaptation of yak lungs to the plateau hypoxic environment. The differences in the distribution and expression of PDK1, HIF-1α, and VEGF may be related to the adaptation of yak lungs to the plateau hypoxic environment, which provides basic information for studying the mechanism of hypoxia adaptation in yaks. ABSTRACT: The aim of this study was to investigate the molecular mechanisms by which hypoxia affects the biological behavior of yak PASMCs, the changes in the histological structure of yak and cattle lungs, and the relationships and regulatory roles that exist regarding the differences in the distribution and expression of PDK1 and its hypoxia-associated factors screened for their role in the adaptation of yak lungs to the plateau hypoxic environment. The results showed that, at the level of transcriptome sequencing, the molecular regulatory mechanisms of the HIF-1 signaling pathway, glucose metabolism pathway, and related factors (HK2/PGK1/ENO1/ENO3/ALDOC/ALDOA) may be closely related to the adaptation of yaks to the hypoxic environment of the plateau; at the tissue level, the presence of filled alveoli and semi-filled alveoli, thicker alveolar septa and basement membranes, a large number of erythrocytes, capillary distribution, and collagen fibers accounted for all levels of fine bronchioles in the lungs of yaks as compared to cattle. A higher percentage of goblet cells was found in the fine bronchioles of yaks, and PDK1, HIF-1α, and VEGF were predominantly distributed and expressed in the monolayers of ciliated columnar epithelium in the branches of the terminal fine bronchioles of yak and cattle lungs, with a small amount of it distributed in the alveolar septa; at the molecular level, the differences in PDK1 mRNA relative expression in the lungs of adult yaks and cattle were not significant (p > 0.05), the differences in HIF-1α and VEGF mRNA relative expression were significant (p < 0.05), and the expression of PDK1 and HIF-1α proteins in adult yaks was stronger than that in adult cattle. PDK1 and HIF-1α proteins were more strongly expressed in adult yaks than in adult cattle, and the difference was highly significant (p < 0.01); the relative expression of VEGF proteins was not significantly different between adult yaks and cattle (p > 0.05). The possible regulatory relationship between the above results and the adaptation of yak lungs to the plateau hypoxic environment paves the way for the regulatory mechanisms of PDK1, HIF-1α, and VEGF, and provides basic information for studying the mechanism of hypoxic adaptation of yaks in the plateau. At the same time, it provides a reference for human hypoxia adaptation and a target for the prevention and treatment of plateau diseases in humans and plateau animals.