Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
Reproduction. 2021 Oct 7;162(5):385-395. doi: 10.1530/REP-21-0181.
The epithelial-to-mesenchymal transition may play a role in adenomyosis. GRIM19 expression is downregulated in adenomyotic lesions, and the effects of this downregulation in adenomyosis remain relatively unclear. In this study, we aimed to explore whether aberrant GRIM19 expression is associated with the epithelial-to-mesenchymal transition in adenomyosis and found that the expression of both GRIM19 and WT1 was low, and epithelial-to-mesenchymal transition, which included significant changes in CDH1, CDH2 and KRT8 expression, occurred in adenomyotic lesions, as confirmed by Western blotting and quantitative real-time PCR. We provided novel insights into WT1 expression in adenomyosis, revealing that WT1 expression was increased in the endometrial glands of adenomyotic lesions by immunohistochemistry. In vitro, knockdown of GRIM19 expression by small interfering RNA (siRNA) promoted the proliferation, migration and invasion of Ishikawa cells, as measured by Cell Counting Kit-8, wound healing assay and Transwell assays. Western blotting and quantitative real-time PCR confirmed that WT1 expression increased and epithelial-to-mesenchymal transition was induced, including the upregulation of CDH2 and downregulation of CDH1 and KRT8after transfecting the GRIM19 siRNA to Ishikawa cells. Furthermore, WT1 expression was upregulated and epithelial-to-mesenchymal transition was observed, including downregulation of CDH1 and KRT8in GRIM19 gene-knockdown mice. Upregulation of Wt1 expression in the endometrial glands of Grim19 knockdown mice was also verified by immunohistochemistry. Taken together, these results reveal that low expression of GRIM19 in adenomyosis may upregulate WT1 expression and induce epithelial-to-mesenchymal transition in the endometria, providing new insights into the pathogenesis of adenomyosis.
上皮-间质转化可能在子宫腺肌病中起作用。GRIM19 表达在子宫腺肌病病变中下调，其下调对子宫腺肌病的影响尚不清楚。在本研究中，我们旨在探讨异常的 GRIM19 表达是否与子宫腺肌病中的上皮-间质转化有关，发现 GRIM19 和 WT1 的表达均较低，并且发生了上皮-间质转化，包括 CDH1、CDH2 和 KRT8 表达的显著变化，这通过 Western blot 和定量实时 PCR 得到证实。我们提供了 WT1 在子宫腺肌病中表达的新见解，发现免疫组织化学染色显示 WT1 在子宫腺肌病病变的子宫内膜腺中表达增加。在体外，通过小干扰 RNA (siRNA) 敲低 GRIM19 表达可通过 Cell Counting Kit-8、划痕愈合试验和 Transwell 试验测量促进 Ishikawa 细胞的增殖、迁移和侵袭。Western blot 和定量实时 PCR 证实，转染 GRIM19 siRNA 后，WT1 表达增加，上皮-间质转化诱导，包括 CDH2 上调和 CDH1 和 KRT8 下调。此外，在 GRIM19 基因敲除小鼠中观察到 WT1 表达上调和上皮-间质转化，包括 CDH1 和 KRT8 下调。通过免疫组织化学染色也验证了 GRIM19 敲低小鼠子宫内膜腺体中 Wt1 表达的上调。总之，这些结果表明，子宫腺肌病中 GRIM19 的低表达可能上调 WT1 表达并诱导子宫内膜的上皮-间质转化，为子宫腺肌病的发病机制提供了新的见解。
