A re-appraisal of mesenchymal-epithelial transition (MET) in endometrial epithelial remodeling.

A re-appraisal of mesenchymal-epithelial transition (MET) in endometrial epithelial remodeling.
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DOI:
10.1007/s00441-022-03711-z
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发表时间:
2023-03
影响因子:
3.6
通讯作者:
--
中科院分区:
生物学3区
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间质上皮转化(MET)是子宫内膜上皮再生的一种机制。它也涉及腺癌和子宫内膜异位症。关于正常子宫生理学中的这一过程知之甚少。以前,使用妊娠和月经样小鼠模型,MET仅作为上皮损伤/修复机制发生。在这里,我们假设MET也发生在损伤/修复之外的其他生理性子宫内膜重塑事件中,例如在发情周期和腺发生(腺体发育)期间。为了研究这一点,使用Amhr 2-Cre-YFP/GFP间充质特异性报告小鼠来追踪间充质衍生(MD)细胞的命运。使用EpCAM(上皮标记物),在产后和处女小鼠中,在除间情期之外的发情周期的所有阶段鉴定EpCAM+YFP+ MD-上皮细胞。EpCAM+YFP+ MD-上皮细胞在雌激素主导的发情前期期间占上皮细胞的80%,并且在间情期显著下降至与对照子宫不可区分,表明MET是经尿道调节的。MD-上皮细胞也确定在出生后上皮重塑。MET在出生后立即发生,在出生后第0.5天(P),EpCAM+GFP+细胞的范围从可忽略的(0.21%)到上皮细胞的82%。EpCAM+GFP+ MD-上皮细胞在腺发生起始期间下降(P8,平均值)。1.75%),在腺体形态发生过程中逐渐升高(P14,avg. 10%)。MD-上皮细胞表达与非MD-上皮细胞共同的标志物(例如,EpCAM、F0XA 2、ESR1、PCR)。然而,MD-上皮细胞的差异调节产后和成人,这表明在两个人口的功能差异。我们得出结论,MET不仅作为上皮损伤/修复机制发生,而且在其他上皮重塑事件中也发生,据我们所知,这在其他组织中尚未得到证实。 在线版本包含补充材料,可通过10.1007/s 00441 -022-03711-z获得。
Mesenchymal-epithelial transition (MET) is a mechanism of endometrial epithelial regeneration. It is also implicated in adenocarcinoma and endometriosis. Little is known about this process in normal uterine physiology. Previously, using pregnancy and menses-like mouse models, MET occurred only as an epithelial damage/repair mechanism. Here, we hypothesized that MET also occurs in other physiological endometrial remodeling events, outside of damage/repair, such as during the estrous cycle and adenogenesis (gland development). To investigate this, Amhr2-Cre-YFP/GFP mesenchyme-specific reporter mice were used to track the fate of mesenchymal-derived (MD) cells. Using EpCAM (epithelial marker), EpCAM+YFP+ MD-epithelial cells were identified in all stages of the estrous cycle except diestrus, in both postpartum and virgin mice. EpCAM+YFP+ MD-epithelial cells comprised up to 80% of the epithelia during estrogen-dominant proestrus and significantly declined to indistinguishable from control uteri in diestrus, suggesting MET is hormonally regulated. MD-epithelial cells were also identified during postnatal epithelial remodeling. MET occurred immediately after birth at postnatal day (P) 0.5 with EpCAM+GFP+ cells ranging from negligible (0.21%) to 82% of the epithelia. EpCAM+GFP+ MD-epithelial cells declined during initiation of adenogenesis (P8, avg. 1.75%) and then increased during gland morphogenesis (P14, avg. 10%). MD-epithelial cells expressed markers in common with non-MD-epithelial cells (e.g., EpCAM, FOXA2, ESR1, PGR). However, MD-epithelial cells were differentially regulated postnatally and in adults, suggesting a functional distinction in the two populations. We conclude that MET occurs not only as an epithelial damage/repair mechanism but also during other epithelial remodeling events, which to our knowledge has not been demonstrated in other tissues. The online version contains supplementary material available at 10.1007/s00441-022-03711-z.
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