Interactions between kidney proteins and metabolism in Tibetan sheep at different altitudes.

When oxygen supply to the kidneys is restricted, it may trigger a series of acid-base imbalances and pathological states, subsequently inducing hypoxic adaptive mechanisms in the kidneys. However, the protein-metabolism interaction mechanisms underlying this process remain unclear. Therefore, this study conducted proteomic and metabolomic analyses on Tibetan sheep kidneys collected at three distinct altitudes (2500 m, 3500 m and 4500 m) to elucidate the protein-metabolism interaction mechanisms during hypoxic adaptation. The results demonstrate a synergistic relationship between proteins and metabolism, revealing dynamic expression patterns. Key DEPs (ALDH2, COX5A, GLUD1, NDUFS2, NDUFS8 and SLC17A1) and key DEMs (Wedelolactone, Cytidine, and 3-hydroxybenzoic acid) primarily participated in the antioxidant defense, anti-inflammatory, and energy supply functions of Tibetan sheep kidney hypoxia adaptation through signaling pathways such as the citrate cycle (TCA cycle) and oxidative phosphorylation. In summary, the adaptive mechanisms to renal hypoxia are not influenced by a single protein or metabolite, but rather are related to the interactions between proteins and metabolites. These interactions may collectively influence the adaptive mechanisms, ensuring that the kidneys maintain normal function in high-altitude environments.