β-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition.
β-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition.
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DOI：
10.1002/path.4224
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发表时间：
2013-10
影响因子：
7.3
通讯作者：
Jeong, Jae-Wook
中科院分区：
文献类型：
--
作者：
Oh, Seo Jin;Shin, Jung-Ho;Kim, Tae Hoon;Lee, Hee Sun;Yoo, Jung-Yoon;Ahn, Ji Yeon;Broaddus, Russell R.;Taketo, Makoto M.;Lydon, John P.;Leach, Richard E.;Lessey, Bruce A.;Fazleabas, Asgerally T.;Lim, Jeong Mook;Jeong, Jae-Wook
子宫腺肌病的定义是子宫内膜腺体和子宫肌层内的间质。尽管其频繁发生，子宫腺肌病的确切病因和病理生理学仍然是未知的。WNT/β-catenin信号传导分子是重要的，并且应该对子宫功能进行严格调节。为了研究β-连环蛋白信号传导在子宫腺肌病中的作用，检测了β-连环蛋白的表达。与对照子宫内膜相比，人子宫腺肌病上皮细胞的细胞核和细胞质β-连环蛋白表达显著升高。为了确定β-连环蛋白在鼠子宫中的组成性激活是否导致子宫腺肌病的发展，通过将PR-Cre小鼠与Ctnnb 1f（ex 3）/+小鼠杂交，使用在子宫中表达显性稳定的β-连环蛋白的小鼠。PRcre/+ Ctnnb 1f（ex 3）/+小鼠的子宫显示出异常的不规则结构和子宫肌层中的高度活跃的增殖，随后发展为子宫腺肌病。有趣的是，与对照小鼠相比，PRcre/+ Ctnnb 1f（ex 3）/+小鼠上皮细胞中E-钙粘蛋白的表达受到抑制。E-钙粘蛋白的抑制是上皮-间充质转化（EMT）的标志之一。在PRcre/+ Ctnnb 1f（ex 3）/+小鼠子宫的一些上皮细胞中观察到SNAIL和ZEB 1的表达，但在对照小鼠中未观察到。PRcre/+ Ctnnb 1f（ex 3）/+小鼠部分上皮细胞表达间充质细胞标志物波形蛋白和COUP-TFII。在人类子宫腺肌病中，上皮细胞中E-cadherin的表达与对照子宫内膜相比降低，而子宫内膜间质标记物CD 10在人类子宫腺肌病的一些上皮细胞中表达。提示β-catenin的异常激活通过诱导EMT参与子宫腺肌病的发生发展。
Adenomyosis is defined by the presence of endometrial glands and stroma within the myometrium. Despite its frequent occurrence, the precise aetiology and physiopathology of adenomyosis is still unknown. WNT/β-catenin signalling molecules are important and should be tightly regulated for uterine function. To investigate the role of β-catenin signalling in adenomyosis, the expression of β-catenin was examined. Nuclear and cytoplasmic β-catenin expression was significantly higher in epithelial cells of human adenomyosis compared to control endometrium. To determine whether constitutive activation of β-catenin in the murine uterus leads to development of adenomyosis, mice that expressed a dominant stabilized β-catenin in the uterus were used by crossing PR-Cre mice with Ctnnb1f(ex3)/+ mice. Uteri of PRcre/+ Ctnnb1f(ex3)/+ mice displayed an abnormal irregular structure and highly active proliferation in the myometrium, and subsequently developed adenomyosis. Interestingly, the expression of E-cadherin was repressed in epithelial cells of PRcre/+ Ctnnb1f(ex3)/+ mice compared to control mice. Repression of E-cadherin is one of the hallmarks of epithelial–mesenchymal transition (EMT). The expression of SNAIL and ZEB1 was observed in some epithelial cells of the uterus in PRcre/+ Ctnnb1f(ex3)/+ mice but not in control mice. Vimentin and COUP-TFII, mesenchymal cell markers, were expressed in some epithelial cells of PRcre/+ Ctnnb1f(ex3)/+ mice. In human adenomyosis, the expression of E-cadherin was decreased in epithelial cells compared to control endometrium, while CD10, an endometrial stromal marker, was expressed in some epithelial cells of human adenomyosis. These results suggest that abnormal activation of β-catenin contributes to adenomyosis development through the induction of EMT.
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影响因子：
6.1
作者：
Bergholt, T;Eriksen, L;Hertz, JB
通讯作者：
Hertz, JB
影响因子：
4.8
作者：
Franco, Heather L.;Dai, Daisy;DeMayo, Francesco J.
通讯作者：
DeMayo, Francesco J.
影响因子：
7.3
作者：
Chen, Yi-Jen;Li, Hsin-Yang;Yang, Muh-Hwa
通讯作者：
Yang, Muh-Hwa
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R
影响因子：
5.7
作者：
Do Trong Khanh;Mekata, Eiji;Tani, Tohru
通讯作者：
Tani, Tohru