Endometrial stromal PRMT5 plays a crucial role in decidualization by regulating NF-κB signaling in endometriosis.
Endometrial stromal PRMT5 plays a crucial role in decidualization by regulating NF-κB signaling in endometriosis.
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子宫内膜基质 PRMT5 通过调节子宫内膜异位症中的 NF-κB 信号在蜕膜化中发挥至关重要的作用
DOI：
10.1038/s41420-022-01196-x
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发表时间：
2022-10-04
影响因子：
7
通讯作者：
Yan, Guijun
中科院分区：
文献类型：
--
作者：
Cai, Xinyu;Xu, Manlin;Zhang, Hui;Zhang, Mei;Wang, Junxia;Mei, Jie;Zhang, Yang;Zhou, Jidong;Zhen, Xin;Kang, Nannan;Yue, Qiuling;Sun, Haixiang;Jiang, Ruiwei;Yan, Guijun
蜕膜化是胚胎着床成功的先决条件，其中细长的成纤维细胞样子宫内膜基质细胞分化为更圆的蜕膜细胞。越来越多的证据强调了在位内膜缺陷在子宫内膜异位症患者不孕中的重要作用。然而，精氨酸甲基化在生理性蜕膜化和病理性蜕膜化缺陷过程中的作用尚不清楚。在这里，我们观察到PRMT 5，主要的II型PRMT，在子宫内膜异位症患者的子宫内膜中，主要是在基质细胞中的表达水平降低。与未蜕膜化状态相比，PRMT 5在人类正常分泌期子宫内膜的基质细胞中以及在正常妊娠小鼠或人工诱导蜕膜化的小鼠的蜕膜中增加。PRMT 5的抑制导致小鼠子宫重量和蜕膜化相关调节因子表达（包括FOXO 1、HOXA 10和WNT 4）以及人子宫内膜基质细胞中IGFBP 1和催乳素水平的显著降低。转录组分析显示PRMT 5活性降低通过诱导p65易位至细胞核而导致NF-κB信号转导激活，这在子宫内膜异位症患者中也观察到。最后，PRMT 5的过表达挽救了子宫内膜异位症患者原代子宫内膜间质细胞中IGFBP 1和催乳素的表达缺陷。我们的研究结果表明，促进PRMT 5可能为治疗不孕妇女（如子宫内膜异位症）的蜕膜化缺陷提供新的治疗策略。
Decidualization is a prerequisite for successful embryo implantation, in which elongated fibroblast-like endometrial stromal cells differentiate into more rounded decidual cells. Accumulating evidence has stressed the important role of the defective eutopic endometrium in infertility in endometriosis patients. However, the role of arginine methylation in the process of physiological decidualization and pathological decidualization defects is not clear. Here, we observed that the expression level of PRMT5, the main type II PRMT, was decreased in the endometrium of endometriosis patients, predominantly in stromal cells. Compared with the undecidualized state, PRMT5 was increased in the stromal cells of normal secretory endometrium in humans and in the decidua of normal pregnant mice or mice with artificially induced decidualization. The inhibition of PRMT5 resulted in a significant decrease in uterine weight and decidualization-related regulator expression, including FOXO1, HOXA10 and WNT4, in mice and IGFBP1 and prolactin levels in human endometrial stromal cells. Transcriptome analysis showed that decreased PRMT5 activity led to NF-κB signaling activation by inducing p65 translocation to the nucleus, which was also observed in endometriosis patients. Finally, overexpression of PRMT5 rescued the defective expression of IGFBP1 and prolactin in primary endometrial stromal cells from endometriosis patients. Our results indicate that promotion of PRMT5 may provide novel therapeutic strategies for the treatment of decidualization defects in infertile women, such as those with endometriosis.
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NF-κB：通过甲基化调节。
影响因子：
11.2
作者：
Lu T;Stark GR
通讯作者：
Stark GR
影响因子：
4
作者：
Bedford, Mark T.
通讯作者：
Bedford, Mark T.
影响因子：
6.7
作者：
Eyster, Kathleen M.;Klinkova, Olga;Hansen, Keith A.
通讯作者：
Hansen, Keith A.
影响因子：
4
作者：
King, AE;Critchley, HOD;Kelly, RW
通讯作者：
Kelly, RW
巨噬细胞中不对称二甲基精氨酸和蛋白质 L-精氨酸甲基转移酶 3 介导的一氧化氮含量减少会诱导滋养层细胞凋亡：这是反复流产的潜在原因。
影响因子：
6.1
作者：
Hao, Fan;Tang, Lin-Chen;Jin, Li-Ping
通讯作者：
Jin, Li-Ping