CSF1-associated decrease in endometrial macrophages may contribute to Asherman's syndrome
CSF1-associated decrease in endometrial macrophages may contribute to Asherman's syndrome
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CSF1相关的子宫内膜巨噬细胞减少可能导致阿舍曼综合征
DOI：
10.1111/aji.13191
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发表时间：
2019-11-03
影响因子：
3.6
通讯作者：
Hu, Yali
中科院分区：
文献类型：
--
作者：
Liu, Dan;Wang, Jiali;Hu, Yali
问题阿什曼综合征（AS）的特征是子宫内膜纤维化导致宫内粘连，并出现月经减少、不孕和反复流产等症状。巨噬细胞是炎症、组织修复、再生和纤维化的关键调节因子。然而，巨噬细胞在AS中的作用尚不清楚。研究方法在月经周期增生后期收集AS患者和对照组的子宫内膜活检。马松三色染色和免疫组织化学检测纤维化和增殖标志物。采用免疫染色和流式细胞术检测巨噬细胞。采用实时荧光定量聚合酶链反应（q-PCR）和免疫组织化学检测CCL2、CSF1、CSF1R和GM-CSF的表达水平。一种分化良好的子宫内膜细胞系Ishikawa （IK）被用于体外研究。从THP-1单核细胞分化的巨噬细胞被IL-4/IL-13极化。将其培养上清（M(IL-4/13)-S）涂于H2O2或博莱霉素损伤的IK细胞。结果AS患者子宫内膜间质被纤维组织取代，细胞增殖减少。AS患者子宫内膜内的巨噬细胞以选择性活化的巨噬细胞为主，其数量明显减少。AS患者的CSF1表达水平降低。M(IL-4/13)-S促进IK细胞生长和迁移，抑制h2o2诱导的细胞凋亡。M(IL-4/13)-S保护IK细胞免受博莱霉素诱导的纤维化。结论巨噬细胞是参与子宫内膜修复和纤维化过程的关键细胞。子宫内膜巨噬细胞数量减少可能与CSF1表达水平降低有关。操纵巨噬细胞的激活/功能可能为AS提供新的治疗靶点。
Problem Asherman's syndrome (AS) is characterized by endometrial fibrosis leading to intrauterine adhesions and symptoms like hypomenorrhea, infertility, and recurrent pregnancy loss. Macrophages are key regulators of inflammation, tissue repair, regeneration, and fibrosis. However, the role of macrophages in AS remains unclear. Method of study Endometrial biopsies of AS patients and controls were collected during the late proliferating phase of menstrual cycle. Fibrosis and proliferation markers were detected by Masson's trichrome staining and immunohistochemistry. Macrophages were examined by immunostaining and flow cytometry. The expression levels of CCL2, CSF1, CSF1R, and GM-CSF were detected by quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry. A well-differentiated endometrial cell line Ishikawa (IK) was used for in vitro studies. Macrophages differentiating from THP-1 monocytic cells were polarized by IL-4/IL-13. Their culture supernatants (M(IL-4/13)-S) were applied to H2O2 or bleomycin-damaged IK cells. Results In AS patients, endometrial stroma was replaced by fibrous tissue and cell proliferation was reduced. Macrophages in endometrial tissue were mainly alternative activated macrophages and their number was significantly decreased in AS patients. The CSF1 expression level was reduced in AS patients. M(IL-4/13)-S promoted the growth and migration of IK cells and inhibited H2O2-induced apoptosis. M(IL-4/13)-S protected IK cells from bleomycin-induced fibrosis. Conclusion Macrophages are critical cells involved in the process of endometrial repair and fibrosis. The decreased amount of endometrial macrophages may be attributed to the reduced expression level of CSF1. Manipulation of macrophage activation/function may provide a novel therapeutic target for AS.