Niclosamide targets the dynamic progression of macrophages for the resolution of endometriosis in a mouse model.
Niclosamide targets the dynamic progression of macrophages for the resolution of endometriosis in a mouse model.
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烟酰胺靶向巨噬细胞的动态进程，以解决小鼠模型中子宫内膜异位症的分辨率。
DOI：
10.1038/s42003-022-04211-0
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发表时间：
2022-11-11
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
鉴于巨噬细胞在子宫内膜异位症发病机制中的重要作用，靶向巨噬细胞可能是一个很有前途的治疗方向。在这里，我们研究了氯硝柳胺对子宫内膜异位症小鼠模型中由巨噬细胞调节失调引起的扰动微环境的疗效。单细胞转录分析显示，小鼠腹腔巨噬细胞的异质性包括三种中间亚型，具有传统的“小”或“大”腹膜巨噬细胞(SPM和LPM)的共同特征。子宫内膜异位症样病变(ELL)促进了巨噬细胞的分化，促进了驻留的LPM的补充，并增加了胚胎来源LPM的消融，而这些LPM被氯硝柳胺逐步抑制。此外，氯硝柳胺恢复了巨噬细胞和B细胞之间的细胞间通讯。因此，氯硝柳胺通过对巨噬细胞动态进程的精细调控，挽救了子宫内膜异位症的扰动微环境。在患者中验证类似的巨噬细胞发病机制将进一步促进氯硝柳胺在子宫内膜异位症治疗中的临床应用。在子宫内膜异位症的小鼠模型中，氯硝柳胺被发现通过精细调节巨噬细胞的动态进展而具有潜在的治疗价值。
Due to the vital roles of macrophages in the pathogenesis of endometriosis, targeting macrophages could be a promising therapeutic direction. Here, we investigated the efficacy of niclosamide for the resolution of a perturbed microenvironment caused by dysregulated macrophages in a mouse model of endometriosis. Single-cell transcriptomic analysis revealed the heterogeneity of macrophages including three intermediate subtypes with sharing characteristics of traditional “small” or “large” peritoneal macrophages (SPMs and LPMs) in the peritoneal cavity. Endometriosis-like lesions (ELL) enhanced the differentiation of recruited macrophages, promoted the replenishment of resident LPMs, and increased the ablation of embryo-derived LPMs, which were stepwise suppressed by niclosamide. In addition, niclosamide restored intercellular communications between macrophages and B cells. Therefore, niclosamide rescued the perturbed microenvironment in endometriosis through its fine regulations on the dynamic progression of macrophages. Validation of similar macrophage pathogenesis in patients will further promote the clinical usage of niclosamide for endometriosis treatment. In a mouse model of endometriosis, niclosamide is found to have potential therapeutic value through its fine regulations of the dynamic progression of macrophages.
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影响因子：
4.8
作者：
Chen W;Mook RA Jr;Premont RT;Wang J
通讯作者：
Wang J
影响因子：
7.3
作者：
Capobianco A;Rovere-Querini P
通讯作者：
Rovere-Querini P
DOI：
10.1073/pnas.0703451104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Hever, Aniko;Roth, Richard B.;Ziotnik, Albert
通讯作者：
Ziotnik, Albert
影响因子：
2
作者：
Gallinelli, A;Chiossi, G;Volpe, A
通讯作者：
Volpe, A
影响因子：
6
作者：
Greaves, Erin;Ternp, Julia;Saunders, Philippa T. K.
通讯作者：
Saunders, Philippa T. K.