IGF2BP2 regulates the proliferation and migration of endometrial stromal cells through the PI3K/AKT/mTOR signaling pathway in Hu sheep

文献类型： 外文期刊

第一作者： Deng, Kaiping

作者： Deng, Kaiping;Li, Xiaodan;Su, Yalong;Sun, Xuan;Wei, Wurilege;Fan, Yixuan;Zhang, Yanli;Wang, Feng;Deng, Kaiping;Li, Xiaodan;Su, Yalong;Sun, Xuan;Fan, Yixuan;Zhang, Yanli;Wang, Feng;Liu, Zhipeng;Wei, Wurilege

作者机构：

关键词： endometrial stromal cells; endometrial function; Hu sheep; IGF2BP2; PI3K/AKT/mTOR pathway

期刊名称：JOURNAL OF ANIMAL SCIENCE （ 影响因子：3.3； 五年影响因子：3.1 ）

ISSN： 0021-8812

年卷期： 2024 年 102 卷

页码：

收录情况： SCI

摘要： Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), a significant member of the conserved RNA-binding protein family, plays various roles in numerous physiological and pathological processes. However, the specific function of IGF2BP2 in regulating endometrial function in sheep remains largely unknown. In this study, we observed a significant upregulation in IGF2BP2 mRNA abundance in the endometrium during the luteal phase compared to the follicular phase in Hu sheep. The knockdown of IGF2BP2 resulted in accelerated cell proliferation and migration of Hu sheep endometrial stromal cells (ESCs). Moreover, RNA sequencing analysis revealed that genes with significantly altered expression in IGF2BP2 knockdown cells were predominantly enriched in endometrial receptivity-related signaling pathways, such as cytokine-cytokine receptor interaction, NOD-like receptor, PI3K-AKT, and JAK-STAT signaling pathway. Additionally, the knockdown of IGF2BP2 significantly increased the expression of matrix metalloprotein 9 (MMP9), vascular endothelial growth factor, and prolactin (PRL) in ESCs. The knockdown of IGF2BP2 was also observed to stimulate the PI3K/AKT/mTOR pathway by upregulating integrin beta 4 (ITGB4) expression. Notably, the downregulation of ITGB4 attenuates IGF2BP2 knockdown-induced facilitation of proliferation and migration of Hu sheep ESCs by inhibiting the PI3K/AKT/mTOR pathway. Collectively, these findings highlight the important role of IGF2BP2 in regulating endometrial function, particularly through the modulation of ESC proliferation and migration via the PI3K/AKT/mTOR pathway. IGF2BP2 was found to be ubiquitously expressed in various reproductive organs, with notably high levels of expression in the endometrium during the luteal phase (LP) in Hu sheep. Moreover, our findings suggest that IGF2BP2 regulates the PI3K/AKT/mTOR signaling pathway by modulating ITGB4 expression, thereby influencing the proliferation and migration of ESCs. The maintenance of normal physiological functionality of the endometrium is crucial for successful embryo implantation. Endometrial stromal cells (ESCs), as the principal components of the endometrium, play a key role in establishing optimal endometrial receptivity for embryo implantation. Despite the well-established role of IGF2BP2 in the pathogenesis of endometriosis in women, its functional impact on endometrial activity in ruminants, particularly in ovine species, remains undefined. In this study, we investigated the expression pattern of IGF2BP2 in the reproductive organs of female sheep and evaluated the potential roles and underlying mechanisms of IGF2BP2 in the function of sheep ESCs. This experiment confirmed the important role of IGF2BP2 in regulating endometrial function by modulating the proliferation and migration of Hu sheep ESCs.

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