酪蛋白激酶 1α 的下调通过磷酸酶和张力蛋白同源物/自噬相关 7 介导的自噬促进子宫内膜异位症。

Down-Regulation of Casein Kinase 1α Contributes to Endometriosis through Phosphatase and Tensin Homolog/Autophagy-Related 7-Mediated Autophagy.

机构信息

Department of Gynaecology and Obstetrics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.

出版信息

Am J Pathol. 2021 Dec;191(12):2195-2202. doi: 10.1016/j.ajpath.2021.08.015.

DOI:10.1016/j.ajpath.2021.08.015

PMID:34809787

Abstract

The present study aimed to explore the roles of casein kinase 1α (CK1α) in endometriosis and its underlying mechanisms. Endometrial specimen were collected from the patients and healthy volunteers. The expression patterns of CK1α, phosphatase and tensin homolog (PTEN), and autophagy-related proteins were determined using immunohistochemistry staining, Western blot analysis, and quantitative RT-PCR. Besides, the CK1α-overexpressing cells and PTEN knockdown cells were constructed in the endometrial stromal cells isolated from endometriosis patients. In addition, the cells were transfected with pcDNA3.1-CK1α or pcDNA3.1-CK1α plus siRNA- PTEN. The expressions of CK1α, PTEN, and autophagy-related proteins were determined using Western blot and quantitative RT-PCR. The expressions of CK1α and autophagy-related 7 (Atg7) were significantly decreased in the ectopic endometrium compared with the eutopic endometrium. Spearman rank correlation analysis revealed positive correlations between CK1α and PTEN, CK1α and Atg7, and PTEN and Atg7. In addition, CK1α, PTEN, and autophagy-related proteins were down-regulated in ectopic endometrium. Interestingly, overexpression of CK1α significantly increased the expressions of autophagy-related proteins, whereas the protein expression of autophagy-related proteins was decreased with PTEN knock-down. CK1α regulated PTEN/Atg7-mediated autophagy in endometriosis.

摘要

本研究旨在探讨酪蛋白激酶 1α（CK1α）在子宫内膜异位症中的作用及其潜在机制。收集患者和健康志愿者的子宫内膜标本。采用免疫组织化学染色、Western blot 分析和定量 RT-PCR 检测 CK1α、磷酸酶和张力蛋白同源物（PTEN）和自噬相关蛋白的表达模式。此外，在从子宫内膜异位症患者分离的子宫内膜基质细胞中构建 CK1α过表达细胞和 PTEN 敲低细胞。此外，用 pcDNA3.1-CK1α 或 pcDNA3.1-CK1α 加 siRNA-PTEN 转染细胞。用 Western blot 和定量 RT-PCR 检测 CK1α、PTEN 和自噬相关蛋白的表达。与在位内膜相比，异位内膜中 CK1α 和自噬相关蛋白 7（Atg7）的表达明显降低。Spearman 秩相关分析显示 CK1α 与 PTEN、CK1α 与 Atg7、PTEN 与 Atg7 之间呈正相关。此外，异位内膜中 CK1α、PTEN 和自噬相关蛋白表达下调。有趣的是，CK1α 的过表达显著增加了自噬相关蛋白的表达，而 PTEN 敲低则降低了自噬相关蛋白的表达。CK1α 调节子宫内膜异位症中 PTEN/Atg7 介导的自噬。