Guo Xiaorong, Fan Xinhao, Xie Chundi, Afe Ayoola Ebenezer, Yang Yalan, Zhou Rong
The State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China; Liaocheng University, Liaocheng, 252059, PR China.
Kunpeng Institute of Modern Agriculture at Foshan, Institute of Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Foshan 528226, PR China.
Int J Biol Macromol. 2025 Jan;284(Pt 1):137785. doi: 10.1016/j.ijbiomac.2024.137785. Epub 2024 Nov 17.
Oxidative stress caused by hypoxia can lead to serious bodily damage and functional degradation. Our previous study in pigs showed that the insulin-like growth factor II receptor (IGF2R) gene might participate in the process of hypoxia adaptability. To investigate the function and mechanism of IGF2R in cellular hypoxia tolerance, we analyze the effect of IGF2R on cell survival capacity under hypoxia conditions in intestinal porcine enterocyte cell line (IPEC-J2) cells. The results show that under hypoxia condition (3% O), cell viability is significantly reduced, the expression of IGF2R and cell apoptosis are significantly increased. Functional analysis suggests that suppressing IGF2R expression under hypoxia does not affect cell cycle and cell proliferation but increases cellular viability. Meanwhile, the expression of the pro-apoptotic gene BAX is reduced, the hypoxia-induced apoptosis is rescued, and cell survival is significantly improved. Transcriptome analysis suggests that global gene expression changes in knockdown IGF2R under hypoxia, IGF2R may regulate apoptosis through oxidative phosphorylation. Our findings demonstrate that suppressing IGF2R expression under hypoxia can rescue hypoxia-induced cell injury by reducing the expression of BAX, highlighting the potential ability of IGF2R regulation for the treatment of hypoxia stress.
缺氧引起的氧化应激可导致严重的身体损伤和功能退化。我们之前在猪身上的研究表明，胰岛素样生长因子II受体（IGF2R）基因可能参与缺氧适应性过程。为了研究IGF2R在细胞缺氧耐受性中的功能和机制，我们分析了IGF2R对猪肠道上皮细胞系（IPEC-J2）细胞在缺氧条件下细胞存活能力的影响。结果表明，在缺氧条件（3% O₂）下，细胞活力显著降低，IGF2R的表达和细胞凋亡显著增加。功能分析表明，在缺氧条件下抑制IGF2R表达不影响细胞周期和细胞增殖，但可提高细胞活力。同时，促凋亡基因BAX的表达降低，缺氧诱导的凋亡得到挽救，细胞存活显著改善。转录组分析表明，在缺氧条件下敲低IGF2R时全局基因表达发生变化，IGF2R可能通过氧化磷酸化调节凋亡。我们的研究结果表明，在缺氧条件下抑制IGF2R表达可通过降低BAX的表达挽救缺氧诱导的细胞损伤，突出了IGF2R调控在治疗缺氧应激方面的潜在能力。
