Physiology and Proteomic Basis of Lung Adaptation to High-Altitude Hypoxia in Tibetan Sheep

SIMPLE SUMMARY: As an indigenous animal living in the Tibetan plateau, the Tibetan sheep is well adapted to high-altitude hypoxia, and the lungs play an important role in overcoming the hypoxic environment. To reveal the physiological and proteomic basis of Tibetan sheep lungs during their adaptation to hypoxia, we studied the lungs of Tibetan sheep at different altitudes using light and electron microscopy and proteome sequencing. The results showed that in the lungs of Tibetan sheep occurred a series of physiological changes with increasing altitude, and some important proteins and pathways identified by proteome sequencing further support these physiology findings. These changes at the physiological and molecular levels may facilitate the adaptation of Tibetan sheep to high-altitude hypoxia. In conclusion, these findings may provide a reference for the prevention of altitude sickness in humans. ABSTRACT: The Tibetan sheep is an indigenous animal of the Tibetan plateau, and after a long period of adaptation have adapted to high-altitude hypoxia. Many physiological changes occur in Tibetan sheep as they adapt to high-altitude hypoxia, especially in the lungs. To reveal the physiological changes and their molecular mechanisms in the lungs of Tibetan sheep during adaptation to high altitudes, we selected Tibetan sheep from three altitudes (2500 m, 3500 m, and 4500 m) and measured blood-gas indicators, observed lung structures, and compared lung proteome changes. The results showed that the Tibetan sheep increased their O(2)-carrying capacity by increasing the hemoglobin (Hb) concentration and Hematocrit (Hct) at an altitude of 3500 m. While at altitude of 4500 m, Tibetan sheep decreased their Hb concentration and Hct to avoid pulmonary hypertension and increased the efficiency of air-blood exchange and O(2) transfer by increasing the surface area of gas exchange and half-saturation oxygen partial pressure. Besides these, some important proteins and pathways related to gas transport, oxidative stress, and angiogenesis identified by proteome sequencing further support these physiology findings, including HBB, PRDX2, GPX1, GSTA1, COL14A1, and LTBP4, etc. In conclusion, the lungs of Tibetan sheep are adapted to different altitudes by different strategies; these findings are valuable for understanding the basis of hypoxic adaptation in Tibetan sheep.