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Hypoxia-Adaptive Protein-Metabolic Interactions in Tibetan Sheep Kidneys

ABSTRACT: this study conducted proteomic and metabolomic analyses on Tibetan sheep kidneys collected at three distinct altitudes (2500m, 3500m and 4500m) to elucidate the protein-metabolism interaction mechanisms during hypoxic adaptation

ORGANISM(S): Ovis Aries

SUBMITTER: Pengfei Zhao

PROVIDER: PXD075530 | iProX | Wed Mar 11 00:00:00 GMT 2026

REPOSITORIES: iProX

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Project description:<p>Gut microbiota plays a significant role in maintaining the homeostasis of the gut internal environment, and the volatile fatty acids (VFAs) produced by it are the main source of energy utilization for the host. The heart, as a key metabolic organ of the body, its energy metabolism efficiency directly affects the body's tolerance to the hypoxic environment at high altitudes. To reveal the dynamic regulatory relationship between the rumen and the heart of Hu sheep during their response to the high-cold and hypoxic environment, this study conducted transcriptome sequencing on the hearts of Hu sheep and Tibetan sheep, and carried out interaction analysis of the differentially expressed genes with rumen microbiota, VFAs, and metabolites. The results showed that: A total of 616 differentially expressed genes (P＜0.05) were identified in the hearts of sheep of different breeds, among which 437 genes were up-regulated and 179 genes were down-regulated. By comparing with known transcription factors, it was found that genes highly expressed in Hu sheep, such as ATP2A3, NPPB, PDE3A, SLC25A4, and AKT3, were significantly enriched in the cGMP-PKG signaling pathway. In the study of the interaction between rumen microbial genera and heart-related differentially expressed genes, it was found that microbial genera such as Candidatus Saccharimonas and Succiniclasticum had a close positive correlation (P＜0.05) with genes related to cardiac energy metabolism; The interaction analysis between the differentially expressed genes and VFAs showed that acetic acid, propionic acid, butyric acid, and valeric acid participated in the regulation of gene expression in a positive and synergistic manner. WGCNA showed that different metabolite modules were concentrated and enriched in Metabolic pathways and participated in the process of cardiac energy metabolism. In addition, metabolites such as Arachidonate, Adenine, and 6-Keto-prostaglandin F1alpha had a positive regulatory relationship with SLC25A4 and AKT3 and were involved in cardiac energy metabolism. This study revealed that Hu sheep can conduct directional regulation of cardiac metabolism through rumen microbiota and metabolites to cope with the hypoxic stress at high altitudes, providing an important reference for a deeper understanding of the response mechanism of Hu sheep to the hypoxic environment at high altitudes.</p>

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Hypoxia-Adaptive Protein-Metabolic Interactions in Tibetan Sheep Kidneys

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