Department of Gynaecology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
BMC Mol Cell Biol. 2022 Aug 6;23(1):37. doi: 10.1186/s12860-022-00426-5.
Endometriosis is one of the most common gynecological diseases, and seriously reduces the quality of life of patients. However, the pathogenesis of this disease is unclear. Therefore, more studies are needed to elucidate its pathogenesis. Our previous publication found that the Sonic Hedgehog (SHH) signaling pathway was activated in endometriosis. This study tested whether SHH signaling in endometrial stromal cells (ESCs) was critical for the pathogenesis of endometriosis.
To examine the effect of inhibiting the SHH signaling pathway on endometriosis, we first isolated ESCs from eutopic endometrial tissues of patients with or without endometriosis and identified the extracted cells by morphological observation and immunofluorescence. Then, we treated ESCs with the GLI inhibitor GANT61 and used CCK-8, wound healing and invasion assays to detect cell activities, such as proliferation, invasion and metastasis. Furthermore, we detected the expression of key proteins and proliferation markers of the SHH signaling pathway in the lesions of nude mice using immunochemistry.
We demonstrated that higher concentrations of GANT61 decreased the proliferation rate and migration distance of ESCs. We observed that GANT61 inhibited the invasion of ESCs. In addition, blockage of the SHH signaling pathway significantly reduced cell proliferation in vitro.
Our study suggested that inhibition of the SHH pathway is involved in cell proliferation and invasive growth in the pathogenesis of endometriosis.
子宫内膜异位症是最常见的妇科疾病之一，严重降低了患者的生活质量。然而，这种疾病的发病机制尚不清楚。因此，需要更多的研究来阐明其发病机制。我们之前的研究发现，Sonic Hedgehog（SHH）信号通路在子宫内膜异位症中被激活。本研究检测了子宫内膜基质细胞（ESCs）中 SHH 信号对子宫内膜异位症发病机制的重要性。
为了研究抑制 SHH 信号通路对子宫内膜异位症的影响，我们首先从有或没有子宫内膜异位症的患者的在位子宫内膜组织中分离出 ESCs，并通过形态观察和免疫荧光鉴定提取的细胞。然后，我们用 GLI 抑制剂 GANT61 处理 ESCs，并用 CCK-8、划痕愈合和侵袭实验检测细胞增殖、侵袭和转移等活性。此外，我们用免疫组化检测了裸鼠病变中 SHH 信号通路的关键蛋白和增殖标志物的表达。
我们证明了较高浓度的 GANT61 降低了 ESCs 的增殖率和迁移距离。我们观察到 GANT61 抑制了 ESCs 的侵袭。此外，阻断 SHH 信号通路显著减少了体外细胞的增殖。
我们的研究表明，抑制 SHH 通路参与了子宫内膜异位症发病机制中的细胞增殖和侵袭性生长。
