Evidence from a mouse model that epithelial cell migration and mesenchymal-epithelial transition contribute to rapid restoration of uterine tissue integrity during menstruation.
Evidence from a mouse model that epithelial cell migration and mesenchymal-epithelial transition contribute to rapid restoration of uterine tissue integrity during menstruation.
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DOI：
10.1371/journal.pone.0086378
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Saunders PT
中科院分区：
文献类型：
--
作者：
Cousins FL;Murray A;Esnal A;Gibson DA;Critchley HO;Saunders PT
对于女性来说，子宫组织结构在每个月经周期都会发生动态变化。月经的特征是子宫内膜上功能层的脱落，是组织功能一系列不可逆变化的最终结果，包括间质蜕膜化、炎症和降解酶的产生。人们对月经期间组织稳态快速恢复的分子机制知之甚少。开发了一种改良的月经小鼠模型，重点关注子宫内膜脱落/修复过程中子宫内膜内发生的事件。黄体酮 (P4) 停药后 4、8、12 和 24 小时评估蜕膜化、阴道出血、组织结构和细胞增殖；小鼠在扑杀前 90 分钟接受单次溴脱氧尿苷 (BrdU) 注射。使用 RT2 PCR 分析仪阵列、qRTPCR 和生物信息学分析确定参与间充质到上皮转化 (MET) 调节的基因表达。小鼠在 P4 停药后 4 至 12 小时内表现出阴道出血，同时伴随着蜕膜细胞团从子宫内膜基底部分脱离。 BrdU 和泛细胞角蛋白的免疫染色揭示了上皮细胞增殖和迁移的证据。在基质隔室内鉴定出似乎从间充质细胞身份转变为上皮细胞身份的细胞。对仅在上皮或基质区室中表达或与 MET 相关的编码基因的 mRNA 进行分析，揭示了表达的动态变化，这与间充质细胞重新编程的作用一致，从而有助于重新上皮化。这些研究为有助于月经后重新上皮化的细胞过程提供了新的见解，涉及上皮细胞迁移和间充质细胞分化以恢复完整上皮细胞层。这些见解可能会为新疗法的开发提供信息，以诱导子宫内膜和其他组织快速愈合，并为遭受大量月经出血的女性带来希望。
In women dynamic changes in uterine tissue architecture occur during each menstrual cycle. Menses, characterised by the shedding of the upper functional layer of the endometrium, is the culmination of a cascade of irreversible changes in tissue function including stromal decidualisation, inflammation and production of degradative enzymes. The molecular mechanisms that contribute to the rapid restoration of tissue homeostasis at time of menses are poorly understood. A modified mouse model of menses was developed to focus on the events occurring within the uterine lining during endometrial shedding/repair. Decidualisation, vaginal bleeding, tissue architecture and cell proliferation were evaluated at 4, 8, 12, and 24 hours after progesterone (P4) withdrawal; mice received a single injection of bromodeoxyuridine (BrdU) 90 mins before culling. Expression of genes implicated in the regulation of mesenchymal to epithelial transition (MET) was determined using a RT2 PCR profiler array, qRTPCR and bioinformatic analysis. Mice exhibited vaginal bleeding between 4 and 12 hours after P4 withdrawal, concomitant with detachment of the decidualised cell mass from the basal portion of the endometrial lining. Immunostaining for BrdU and pan cytokeratin revealed evidence of epithelial cell proliferation and migration. Cells that appeared to be in transition from a mesenchymal to an epithelial cell identity were identified within the stromal compartment. Analysis of mRNAs encoding genes expressed exclusively in the epithelial or stromal compartments, or implicated in MET, revealed dynamic changes in expression, consistent with a role for reprogramming of mesenchymal cells so that they could contribute to re-epithelialisation. These studies have provided novel insights into the cellular processes that contribute to re-epithelialisation post-menses implicating both epithelial cell migration and mesenchymal cell differentiation in restoration of an intact epithelial cell layer. These insights may inform development of new therapies to induce rapid healing in the endometrium and other tissues and offer hope to women who suffer from heavy menstrual bleeding.
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影响因子：
3.8
作者：
Collins, Frances;MacPherson, Sheila;Saunders, Philippa T. K.
通讯作者：
Saunders, Philippa T. K.
影响因子：
4
作者：
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作者：
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影响因子：
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作者：
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通讯作者：
Critchley, Hilary O. D.
影响因子：
6.1
作者：
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通讯作者：
Courtoy, PJ