Hypo-Expression of Tuberin Promotes Adenomyosis via the mTOR1-Autophagy Axis.
Hypo-Expression of Tuberin Promotes Adenomyosis via the mTOR1-Autophagy Axis.
复制标题
马铃薯蛋白的低表达通过 mTOR1-自噬轴促进子宫腺肌病
DOI：
10.3389/fcell.2021.710407
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Gu NH;Li GJ;Yang BX;You M;Lin Y;Sun F;Xu H
子宫腺肌病（AM）是一种子宫内膜组织侵入子宫肌层的疾病，在育龄妇女中的患病率为10-60%。TSC 2通过mTOR 1信号传导调节结直肠癌和子宫内膜癌中的自噬。自噬失调与子宫腺肌病发病机制有关。然而，TSC 2是否通过自噬参与子宫腺肌病仍然不清楚。在此，我们发现分泌期子宫腺肌病中TSC 2的表达明显低于正常子宫内膜。此外，TSC 2和自噬标记物的表达在异位病变中显著低于在位样本。TSC 2下调通过mTOR 1信号通路激活子宫内膜细胞抑制自噬，导致过度增殖，迁移和EMT; TSC 2过表达诱导相反的效果。雷帕霉素处理抑制细胞增殖，迁移和EMT在缺乏TSC 2。与此同时，自噬特异性抑制剂（SAR-405）恢复了TSC 2敲低石川细胞中雷帕霉素处理下的迁移和EMT。最后，SAR-405处理促进EMT和过表达细胞的迁移。总的来说，我们的研究结果表明，TSC 2控制子宫内膜上皮细胞迁移和EMT通过调节mTOR 1-自噬轴激活和低表达的TSC 2在子宫内膜可能会促进子宫腺肌病。
Adenomyosis (AM) is a disease in which endometrial tissue invades the myometrium and has a 10–60% prevalence in reproductive-aged women. TSC2 regulates autophagy via mTOR1 signalling in colorectal cancer and endometrial carcinoma. Dysregulation of autophagy is implicated in adenomyosis pathogenesis. However, whether TSC2 participates in adenomyosis via autophagy remains obscure. Here, we found that the expression of TSC2 in adenomyosis was significantly decreased than that in normal endometrium during the secretory phase. Moreover, TSC2 and autophagy marker expression was significantly lower in ectopic lesions than in eutopic samples. TSC2 downregulation inhibited autophagy through mTOR1 signalling pathway activation in endometrial cells, leading to excessive proliferation, migration, and EMT; TSC2 overexpression induced the opposite effects. Rapamycin treatment suppressed cell proliferation, migration and EMT in the absence of TSC2. In parallel, an autophagy-specific inhibitor (SAR-405) restored migration and EMT under rapamycin treatment in TSC2-knockdown Ishikawa cells. Finally, SAR-405 treatment promoted EMT and migration of overexpressing cells. Collectively, our results suggest that TSC2 controls endometrial epithelial cell migration and EMT by regulating mTOR1-autophagy axis activation and that hypo-expression of TSC2 in the endometrium might promote adenomyosis.
登录
查看更多内容
影响因子：
81.5
作者：
Henske, Elizabeth P.;Jozwiak, Sergiusz;Thiele, Elizabeth A.
通讯作者：
Thiele, Elizabeth A.
影响因子：
7.3
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
通讯作者：
Jeong, Jae-Wook
影响因子：
7.3
作者：
Chen, Yi-Jen;Li, Hsin-Yang;Yang, Muh-Hwa
通讯作者：
Yang, Muh-Hwa
反复着床失败的女性中分泌期子宫内膜中 PECAM1 介导的 TGF-β 1 表达降低
影响因子：
6.1
作者：
Guo, Feng;Si, Chenchen;Zhang, Aijun
通讯作者：
Zhang, Aijun
影响因子：
11.5
作者：
Lu, Karen H.;Wu, Weiguo;Walker, Cheryl Lyn
通讯作者：
Walker, Cheryl Lyn