Snail在着床、内膜重建、异位症中的功能及作用机制

批准号:
31501206
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
梁晓欢
依托单位:
学科分类:
C1207.受精、着床及母胎互作
结题年份:
2018
批准年份:
2015
项目状态:
已结题
项目参与者:
刘极龙、梁宇翔、刘跃芳、李舒芸
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中文摘要
作为转录因子,Snail参与调控多种生物学过程,尤其在细胞的上皮-间充质两种状态转换的过程中发挥重要作用(EMT或MET)。我们已报道Snail在早期妊娠子宫中具有时空特异性的表达定位,但其在着床及蜕膜化过程中的功能仍不清楚。子宫内膜是个动态变化的组织,有研究报道,在子宫内膜的重建过程中,基质细胞通过MET参与上皮细胞的重建,在子宫内膜异位症的发病过程中,可能发生MET及EMT样的变化。但还不清楚Snail是否参与了内膜重建及内异症的调节。本课题将利用Snail子宫内条件敲除鼠等模型,研究Snail敲除鼠的着床、蜕膜化是否受到影响,以及Snail在内膜重建、子宫内膜异位症中的作用及调控机制。通过研究,阐述Snail调控胚胎着床的作用及机制,初步探讨Snail与内膜重建、内异症的相关性,以及将其作为治疗靶点的可能性。项目研究结果将对临床上不育及相关疾病治疗手段的选择具有重要的价值。
英文摘要
Snail is a critical transcription factor of multiple biological processes, especially during the interconversion between epithelial and mesenchymal cells transition (EMT or MET). Endometrium is dynamic during menstrual/estrus cycle or pregnancy. It's reported that Snail shows temporally and spatially-specific expression pattern during early pregnancy, however its functions during implantation and decidualization are still not completely defined. During the processes of endometrium regeneration, the epithelial tissue regeneration is accomplished by MET. In the aspects of endometriosis, MET and EMT might be involved. Whether Snail is involved in these processes is still not clear. This project will utilize uterus conditional Snail knockout mice to study the following aspects: whether implantation and decidualization fails in Snail cKO mice; whether Snail involves in the processes of endometrium regeneration or endometriosis The results will reveal the scientific basis for the function and mechanism of Snail during embryo implantation; present deeper insight regarding the relationship between Snail and endometrial regeneration and endometriosis, and the possibility of Snail as a target. The information could have important diagnostic and therapy value to inform clinical infertility and related diseases.
在小鼠和人的着床和蜕膜化过程中都伴随着非常明显的基质-上皮转化过程。Snail作为上皮-间充质两种状态转换的过程中重要的转录因子,其在生殖过程中的生理功能还不是很清楚。本课题将利用Snail子宫内条件敲除鼠等模型,研究Snail敲除鼠的着床、蜕膜化是否受到影响,发现在接受态建立的过程中,Lif的表达显著下调,且在上皮细胞中敲除Lif下游的Stat3导致着床失败,因此Snail可能参与Lif-Stat3信号途径调节着床过程。在人的蜕膜化过程中,我们利用RNA-Seq、ChIP-Seq等多种手段证实Snail在基质-上皮化过程中显著上调,且这一过程伴随着增强子图谱的显著变化。项目研究结果将对临床上不育及相关疾病治疗手段的选择具有重要的价值。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Progesterone induces the expression of lipocalin-2 through Akt-c-Myc pathway during mouse decidualization
黄体酮在小鼠蜕膜化过程中通过 Akt-c-Myc 通路诱导 lipocalin-2 的表达
DOI:10.1002/1873-3468.12304
发表时间:2016-08-01
期刊:FEBS LETTERS
影响因子:3.5
作者:Liu, Yue-Fang;Deng, Wen-Bo;Liang, Xiao-Huan
通讯作者:Liang, Xiao-Huan
Molecular characterization of lysyl oxidase-mediated extracellular matrix remodeling during mouse decidualization
小鼠蜕膜化过程中赖氨酰氧化酶介导的细胞外基质重塑的分子特征
DOI:10.1002/1873-3468.12645
发表时间:2017-05-01
期刊:FEBS LETTERS
影响因子:3.5
作者:Li, Shu-Yun;Yan, Jia-qi;Liang, Xiao-Huan
通讯作者:Liang, Xiao-Huan
单细胞转录组解析子宫内膜癌细胞亚群及机理
- 批准号:--
- 项目类别:省市级项目
- 资助金额:10.0万元
- 批准年份:2021
- 负责人:梁晓欢
- 依托单位:
HMGB1缺失后巨噬细胞过量聚集引起胚胎着床失败的表观调控机制
- 批准号:--
- 项目类别:省市级项目
- 资助金额:10.0万元
- 批准年份:2019
- 负责人:梁晓欢
- 依托单位:
国内基金
海外基金
