Analysis of the TGF-β1 of a Tibetan Plateau Schizothoracine Fish (Gymnocypris dobula) Revealed Enhanced Cytoprotection in Hypoxic Environments

<b>Background:</b> The Tibetan Plateau, which is known for its high elevation and low oxygen levels, presents a challenging environment for its inhabitants. To adapt to these hypoxic conditions, species of <i>Schizothoracine</i>, a subfamily of <i>Cyprinidae</i>, have developed unique physiological mechanisms and functions. Transforming growth factor-β (TGF-β) is a multifunctional cytokine involved in the regulation of cell growth, differentiation, apoptosis, and the cellular immune response. However, its specific role in adaptation to hypoxia remains poorly understood. <b>Methods:</b> In this study, we aimed to characterize the TGF-β1 gene in <i>Gymnocypris dobula</i> (<i>Gd</i>) and <i>Schizothorax prenanti</i> (<i>Sp</i>) and to test whether TGF-β1 contributes to hypoxia adaptation in plateau <i>Schizothoracine</i> fish. The predicted protein for <i>Gd</i>-TGF-β1 contains several primary domains, including cwf21 (cdc5 protein 21), GYF (Glycine-Tyrosine-Phenylalanine), FN1 (Fibronectin 1), a conservative domain, and a signal peptide. <b>Results:</b> The results of tissue distribution revealed that the mRNA level of TGF-β1 in brain, heart, muscle, skin, gills, and spleen-which are key tissues involved in oxygen sensing, transport, and physiological adaptation to hypoxic environments-was significantly lower in <i>G. dobula</i> than that in <i>S. prenanti</i>. Western blotting analysis revealed that the expression of activated TGF-β1 in <i>G. dobula</i> was significantly higher than that in <i>S. prenanti</i>. To investigate whether TGF-β1 in <i>G. dobula</i> possesses hypoxic adaptive features, <i>Gd</i>-TGF-β1 and <i>Sp</i>-TGF-β1 were cloned into an expression vector and transfected into 293-T cells, which are widely used due to their ease of culture, high transfectability, and well-characterized properties. We found that the survival rate of cells transfected with <i>Gd</i>-TGF-β1 was significantly higher than that of cells transfected with <i>Sp</i>-TGF-β1 after hypoxia treatment. <b>Conclusions:</b> These findings suggest that <i>G. dobula</i> may promote hypoxic adaptation through the activation and increased expression of TGF-β1. Changes in TGF-β1 expression may play a role in the adaptation of <i>G. dobula</i> to hypoxic conditions.