College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Sci Rep. 2024 Aug 29;14(1):20124. doi: 10.1038/s41598-024-70510-7.
Tibetan pigs are a unique swine strain adapted to the hypoxic environment of the plateau regions in China. The unique mechanisms underlying the adaption by Tibetan pigs, however, are still elusive. Only few studies have investigated hypoxia-associated molecular regulation in the lung tissues of animals living in the plateau region of China. Our previous study reported that ssc-miR-101-3p expression significantly differed in the lung tissues of Tibetan pigs at different altitudes, suggesting that ssc-miR-101-3p plays an important role in the adaptation of Tibetan pigs to high altitude. To understand the underlying molecular mechanism, in this study, the target genes of ssc-miR-101-3p and their functions were analyzed via various methods including qRT-PCR and GO and KEGG pathway enrichment analyses. The action of ssc-miR-101-3p was investigated by culturing alveolar type-II epithelial cells (ATII) of Tibetan pigs under hypoxic conditions and transfecting ATII cells with vectors overexpressing or inhibiting ssc-miR-101-3p. Overexpression of ssc-miR-101-3p significantly increased the proliferation of ATII cells and decreased the expression of inflammatory and apoptotic factors. The target genes of ssc-miR-101-3p were significantly enriched in FOXO and PI3K-AKT signaling pathways required to mitigate lung injury. Further, FOXO3 was identified as a direct target of ssc-miR-101-3p. Interestingly, ssc-miR-101-3p overexpression reversed the damaging effect of FOXO3 in the ATII cells. In conclusion, ssc-miR-101-3p targeting FOXO3 could inhibit hypoxia-induced apoptosis and inflammatory response in ATII cells of Tibetan pigs. These results provided new insights into the molecular mechanisms elucidating the response of lung tissues of Tibetan pigs to hypoxic stress.
藏猪是一种适应中国高原地区低氧环境的独特猪种。然而，藏猪适应低氧环境的独特机制仍不清楚。只有少数研究调查了生活在中国高原地区的动物肺组织中与缺氧相关的分子调控。我们之前的研究报告表明，不同海拔藏猪肺组织中 ssc-miR-101-3p 的表达存在显著差异，提示 ssc-miR-101-3p 在藏猪适应高原环境中发挥重要作用。为了了解潜在的分子机制，本研究通过 qRT-PCR 及 GO 和 KEGG 通路富集分析等多种方法分析了 ssc-miR-101-3p 的靶基因及其功能。通过在缺氧条件下培养藏猪肺泡 II 型上皮细胞（ATII）并转染过表达或抑制 ssc-miR-101-3p 的载体，研究了 ssc-miR-101-3p 的作用。ssc-miR-101-3p 的过表达显著增加了 ATII 细胞的增殖，降低了炎症和凋亡因子的表达。ssc-miR-101-3p 的靶基因显著富集在减轻肺损伤所必需的 FOXO 和 PI3K-AKT 信号通路中。进一步鉴定出 FOXO3 是 ssc-miR-101-3p 的直接靶基因。有趣的是，ssc-miR-101-3p 的过表达逆转了 FOXO3 在 ATII 细胞中的损伤作用。总之，ssc-miR-101-3p 靶向 FOXO3 可抑制藏猪 ATII 细胞缺氧诱导的凋亡和炎症反应。这些结果为阐明藏猪肺组织对低氧应激反应的分子机制提供了新的见解。
