Department of Biomedical Sciences, Catholic Kwandong University, Gangneung, Republic of Korea.
Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
J Cell Physiol. 2018 Apr;233(4):3141-3151. doi: 10.1002/jcp.26151. Epub 2017 Nov 10.
Chemokines play an important role in regulating the complex immune system at the maternal-fetal interface during pregnancy. Among various chemokines, CC motif chemokine ligand 2 (CCL2) plays a role in the recruitment of immune regulatory cells to implantation sites within the endometrium. In cattle, CCL2 is abundantly expressed in the uterine endometrium. However, its intracellular signaling has not been identified. In this study, we examined the effects of CCL2 on bovine endometrial (BEND) cell proliferation. CCL2 stimulated BEND cell proliferation by abundant expression of PCNA, accumulation of cells in the G2/M phase, and activation of the PI3 K/AKT and MAPK signaling pathways. Moreover, CCL2 reduced endoplasmic reticulum stress and restored the inflammation-induced reduction in BEND cell proliferation by regulating the unfolded protein response genes and cytokines. Collectively, these results demonstrated that CCL2 plays a pivotal role in reproductive tissues and may support maternal-fetal interface to improve efficiency of pregnancy.
趋化因子在妊娠期间调节母体-胎儿界面复杂免疫系统中发挥重要作用。在各种趋化因子中，C 型趋化因子配体 2（CCL2）在招募免疫调节细胞到子宫内膜中的植入部位中发挥作用。在牛中，CCL2 在子宫子宫内膜中大量表达。然而，其细胞内信号尚未确定。在这项研究中，我们研究了 CCL2 对牛子宫内膜（BEND）细胞增殖的影响。CCL2 通过大量表达 PCNA、细胞在 G2/M 期的积累以及 PI3K/AKT 和 MAPK 信号通路的激活来刺激 BEND 细胞增殖。此外，CCL2 通过调节未折叠蛋白反应基因和细胞因子减少内质网应激，并恢复炎症引起的 BEND 细胞增殖减少。总之，这些结果表明 CCL2 在生殖组织中发挥关键作用，并可能支持母体-胎儿界面以提高妊娠效率。
