SHH信號通路抑制劑對子宮內膜異位癥患者子宮內膜細胞的影響

2022年8月。哈爾濱醫科大學**附屬醫院婦科（Department of Gynaecology, The First Afliated Hospital of Harbin Medical

University, Harbin, China ）Liyuan Sun and Guangmei Zhang研究團隊在《BMC Molecular andCell Biology》，發表論文標題為：“Effects of an inhibitor of the SHH signaling pathway on endometrial cells of patients with endometriosis”

“SHH信號通路抑制劑對子宮內膜異位癥患者子宮內膜細胞的影響”

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

Our study suggested that inhibition of the SHH pathway is involved in cell proliferation and invasive growth in the pathogenesis of endometriosis.

摘要

背景：子宮內膜異位癥是最常見的婦科疾病之一，嚴重降低了患者的生活質量。然而，該病的發病機制尚不清楚。因此，其發病機制尚需進一步研究。我們之前的研究發現，Sonic Hedgehog (SHH)信號通路在子宮內膜異位癥中被激活。本研究測試了SHH信號在子宮內膜間質細胞(ESCs)中是否對子宮內膜異位癥的發病至關重要。

方法：為了研究抑制SHH信號通路對子宮內膜異位癥的影響，我們首先從子宮內膜異位癥患者和非子宮內膜異位癥患者的異位子宮內膜組織中分離ESCs，并通過形態學觀察和免疫熒光對提取的細胞進行鑒定。然后，我們用GLI抑制劑GANT61處理ESCs，并使用CCK-8，傷口愈合和侵襲試驗檢測細胞活性，如增殖，侵襲和轉移。此外，我們利用免疫化學方法檢測了SHH信號通路關鍵蛋白和增殖標志物在裸鼠病變中的表達。

結果：結果表明，較高濃度的GANT61降低了內皮細胞的增殖速率和遷移距離。我們觀察到GANT61抑制了ESCs的侵襲。此外，在體外實驗中，SHH信號通路的阻斷顯著降低了細胞增殖。

結論：我們的研究提示SHH通路的抑制參與了子宮內膜異位癥的細胞增殖和侵襲性生長。

該論文中，ESCs細胞的體外培養是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯系北京締一生物400-166-8600.

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