Suppressing IGF2R mitigates hypoxia-induced apoptosis by reducing the expression of pro-apoptotic factor BAX.

Abstract

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% O2), 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 results 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.