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由雌激素调节的S100A8通过促进紧密连接形成和基质细胞转化来改善受损的子宫内膜上皮重建。

S100A8 regulated by estrogen improves injured endometrial epithelium reconstruction by promoting tight junction formation and stromal cell transformation.

作者信息

Li Xiaodan, Jia Fang, Bai Huiwen, Chen Xuejing, Zhang Yue, Zhang Ningfang, Yang Hongxin

机构信息

College of Basic Medicine, Inner Mongolia Medical University, Hohhot, China.

First Clinical Medical College, Inner Mongolia Medical University, Hohhot, China.

出版信息

Sci Rep. 2025 Jul 1;15(1):21506. doi: 10.1038/s41598-025-08530-0.

DOI:10.1038/s41598-025-08530-0
PMID:40596550
Abstract

Estrogen is used for endometrial repair; however, it has limited effectiveness. Cytokine S100A8 expression is affected by estrogen and is involved in regulating the damage repair. We aimed to confirm the effects of S100A8 and explore its mechanisms during the reconstruction of the injured endometrium. We investigated the effects of estrogen on S100A8 expression in healthy endometrium. A rat model of endometrial injury and cultured primary endometrial cells were used to determine the pleiotropic effects of S100A8 on endometrial epithelial repair. Estrogen regulated the recruitment of S100A8-positive immune cells (S100A8-PICs) and the release of S100A8 in the healthy endometrium, but estrogen plays a limited role in regulating seriously injured endometrium via self-S100A8. S100A8 administration to the uterine cavity significantly improved the morphology of injured epithelium; influenced the reverse migration of S100A8-PICs; and promoted epithelial localization of proliferating cells, cell junction formation, and transformation of stromal cells to epithelial cells. S100A8 in the uterine cavity has pleiotropic effects that improve endometrial epithelial reconstruction and can compensate for the deficiency in estrogen repair regulation.

摘要

雌激素用于子宫内膜修复;然而,其效果有限。细胞因子S100A8的表达受雌激素影响,并参与调节损伤修复。我们旨在确认S100A8的作用,并探索其在受损子宫内膜重建过程中的机制。我们研究了雌激素对健康子宫内膜中S100A8表达的影响。利用大鼠子宫内膜损伤模型和原代培养的子宫内膜细胞,确定S100A8对子宫内膜上皮修复的多效性作用。雌激素调节健康子宫内膜中S100A8阳性免疫细胞(S100A8-PICs)的募集和S100A8的释放,但雌激素通过自身S100A8对严重受损子宫内膜的调节作用有限。向子宫腔内施用S100A8可显著改善受损上皮的形态;影响S100A8-PICs的逆向迁移;并促进增殖细胞的上皮定位、细胞连接形成以及基质细胞向上皮细胞的转化。子宫腔内的S100A8具有多效性作用,可改善子宫内膜上皮重建,并可弥补雌激素修复调节的不足。

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本文引用的文献

1
Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration.基于脱细胞羊膜的多谱系人子宫内膜类器官用于子宫内膜再生。
Cell Transplant. 2023 Jan-Dec;32:9636897231218408. doi: 10.1177/09636897231218408.
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S100A9 is indispensable for survival of pneumococcal pneumonia in mice.S100A9 对于肺炎链球菌性肺炎小鼠的存活是必不可少的。
PLoS Pathog. 2023 Jul 19;19(7):e1011493. doi: 10.1371/journal.ppat.1011493. eCollection 2023 Jul.
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Repairing and Regenerating Injured Endometrium Methods.修复和再生受损子宫内膜的方法。
Reprod Sci. 2023 Jun;30(6):1724-1736. doi: 10.1007/s43032-022-01108-5. Epub 2023 Jan 18.
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Single-cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation.单细胞 RNA 测序和谱系追踪证实间充质到上皮转化(MET)有助于月经时子宫内膜的修复。
Elife. 2022 Dec 16;11:e77663. doi: 10.7554/eLife.77663.
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Role of S100A8/A9 in Platelet-Neutrophil Complex Formation during Acute Inflammation.S100A8/A9 在急性炎症中血小板-中性粒细胞复合物形成中的作用。
Cells. 2022 Dec 6;11(23):3944. doi: 10.3390/cells11233944.
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Novel Functional Peptide for Next-Generation Vital Pulp Therapy.用于下一代活髓治疗的新型功能肽。
J Dent Res. 2023 Mar;102(3):322-330. doi: 10.1177/00220345221135766. Epub 2022 Nov 22.
7
Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on Monocytes.令人警醒与镇静:S100A8/S100A9 二聚体和四聚体对单核细胞的相反作用。
Adv Sci (Weinh). 2022 Dec;9(36):e2201505. doi: 10.1002/advs.202201505. Epub 2022 Oct 30.
8
S100A8 accelerates wound healing by promoting adipose stem cell proliferation and suppressing inflammation.S100A8通过促进脂肪干细胞增殖和抑制炎症来加速伤口愈合。
Regen Ther. 2022 Jul 15;21:166-174. doi: 10.1016/j.reth.2022.06.010. eCollection 2022 Dec.
9
Murine burn lesion model for studying acute and chronic wound infections.用于研究急性和慢性伤口感染的鼠烧伤损伤模型。
APMIS. 2022 Jul;130(7):477-490. doi: 10.1111/apm.13228. Epub 2022 May 16.
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Cells. 2022 Jan 11;11(2):236. doi: 10.3390/cells11020236.