Transcriptome and Metabolome Integration Provides New Insights into the Regulatory Networks of Tibetan Pigs Alveolar Type II Epithelial Cells in Response to Hypoxia

Tibetan pigs have widespread distribution in plateau environments, and exhibit striking physiological and phenotypic differences from others to adapt to hypoxia conditions. However, the regulation of mRNA and metabolites, as well as function in alveolar type II epithelial cells (ATII) of Tibetan pigs remain undefined. Herein, we carried out an integrated metabolomic and transcriptomic profiling for ATII between Tibetan pigs and Landrace pigs across different oxygen levels to delineate their signature pathways. We observed that metabolite profiles and different expressed genes (DEGs) displayed marked synergy for hypoxia related signature pathways according to Tibetan pigs and Landrace pigs. A total of 546 hypoxia related DEGs and 240 metabolites were uncovered from normoxic (TN and TL) and hypoxic (TL and LL) groups. Functional enrichment assessment indicated that the source hypoxia genes and metabolites were primarily engaged in glycolysis and aldosterone synthesis and secretion. We subsequently constructed the interaction network of mRNA and metabolites related to hypoxia, such as Guanosine-3', 5'-cyclic monophosphate, Gly-Tyr, and phenylacetylglycine. These results indicated that MAPK signaling, aldosterone synthesis and secretion, and different regulated of MCM and adenosine may play vital roles of Tibetan pigs adapt to hypoxic environments better than Landrace pigs. This work provide a perspective and enhances our understanding of mRNA and metabolites that are activated in response to hypoxia in ATII of Tibetan pigs.