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

Background

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 Schizothoracine, a subfamily of Cyprinidae, 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.

Methods

In this study, we aimed to characterize the TGF-β1 gene in Gymnocypris dobula (Gd) and Schizothorax prenanti (Sp) and to test whether TGF-β1 contributes to hypoxia adaptation in plateau Schizothoracine fish. The predicted protein for Gd-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.

Results

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 G. dobula than that in S. prenanti. Western blotting analysis revealed that the expression of activated TGF-β1 in G. dobula was significantly higher than that in S. prenanti. To investigate whether TGF-β1 in G. dobula possesses hypoxic adaptive features, Gd-TGF-β1 and Sp-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 Gd-TGF-β1 was significantly higher than that of cells transfected with Sp-TGF-β1 after hypoxia treatment.

Conclusions

These findings suggest that G. dobula 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 G. dobula to hypoxic conditions.