Abstract：Under hypoxic stress, transforming growth factors-β1 (TGF-β1)/Smad signaling pathway can be activated and caused the occurrence of hypoxic pulmonary hypertension by promoting the proliferation of pulmonary smooth muscle cells. In this study, qPCR was used to detect the relative expression levels of TGF-β1, Smad2 and Smad3 genes in the lung tissues of newborn, juvenile, adult and aged yak (Bos grunniens). The protein expression levels of TGF-β1, Smad2 and Smad3, the phosphorylated protein levels of Smad2/Smad3 (P-Smad2/Smad3) and their distribution characteristics in the lung tissues of newborn, juvenile, adult and aged yak were analyzed by Western blot and immunohistochemistry method. The results of qPCR and Western blot showed that the expression trends of TGF-β1, Smad2, Smad3 and P-Smad2/Smad3 were basically the same, and there were differences in expression in the lung tissue of yak in the newborn, juvenile, adult and aged groups, and the expression levels were higher in the lung tissue of the newborn and adult yak groups, which was significantly higher than that in the yak lung tissue of the juvenile and aged groups (P<0.05). The results of immunohistochemistry showed that the distribution of TGF-β1, Smad2, Smad3 and P-Smad2/Smad3 was basically the same, mainly distributed in tracheal epithelial cells, pulmonary artery endothelial cells and alveolar type Ⅱ epithelial cells in the lungs of newborn, juvenile, adult and aged yaks, the positive expression was also found in lung trachea wall smooth muscle cells and pulmonary artery smooth muscle cells in newborn, adult and aged yaks. This study found that TGF-β1/Smad signal pathway was activated during hypoxic adaptation in yak lungs, and there were significant differences in expression activity among newborn, juvenile, adult and aged yak lungs, the expression activity was higher in the newborn group, significantly down-regulated in the young group, the highest in the adult group, and decreased in the old group. These results showed that the dynamic regulation of TGF-β1/Smad signaling pathway could be involved in the formation of hypoxia adaptive structure and the maintenance of pulmonary vascular function in yaks. The results provide data for further study on the mechanism of lung hypoxia adaptation in yaks.
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