Ectopic Endometrial Cell-Derived Exosomal Moesin Induces Eutopic Endometrial Cell Migration, Enhances Angiogenesis and Cytosolic Inflammation in Lesions Contributes to Endometriosis Progression.
Ectopic Endometrial Cell-Derived Exosomal Moesin Induces Eutopic Endometrial Cell Migration, Enhances Angiogenesis and Cytosolic Inflammation in Lesions Contributes to Endometriosis Progression.
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异位子宫内膜细胞衍生的外泌体 Moesin 诱导在位子宫内膜细胞迁移，增强病变中的血管生成和细胞溶质炎症，有助于子宫内膜异位症的进展
DOI：
10.3389/fcell.2022.824075
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
背景：子宫内膜异位症（Endometriosis，EMs）是最常见的妇科疾病，其病因和/或病理生理机制至今仍不清楚。最近的研究表明，细胞外囊泡（EV），特别是外泌体，在发展各种临床疾病中起着关键作用。然而，外泌体在子宫内膜异位症进展中的意义尚未得到很好的阐明。 方法：通过transwell测定、划痕试验、管形成测定、蛋白质印迹和qRT-PCR分析评估异位基质细胞外泌体（eEV）。通过质谱分析从EMS患者和健康供体收集的子宫内膜组织和阴道分泌物中的外泌体的蛋白质表达谱。利用siRNA干扰技术抑制exosomal蛋白的表达，进行体内功能分析。最后，进行体外实验以验证我们在EMs小鼠模型中观察到的结果。 结果：在体外，我们发现eEV通过上调MMP 9的表达和活性来改善NSC的迁移能力。根据我们的研究结果，eEV还有助于血管生成，并提高卵巢上皮细胞中炎症细胞因子的表达。ESC外泌体中的膜突蛋白（MSN）水平显著高于NSC外泌体（1.22e8±5.58e6对比6.605e7±4.574e6，LFQ强度），如蛋白质质谱和生物信息学分析所示。在异位基质细胞中，ER α受体刺激RhoA/Rock-2/MSN通路。我们发现，下调外泌体膜突蛋白减少了NSC迁移（约3倍变化）和MMP 9表达（约2倍变化）。另一方面，Exomsni抑制血管生成和炎性细胞因子释放。免疫组织化学和免疫荧光结果表明，外泌体MSN显著改变了多克隆病变中MM 9、VEGFR和p-VEGFR的表达。此外，我们发现周围组织中促炎因子的表达升高。 结论：来源于异位基质细胞的外泌体MSN可通过介导异位环境中“迁移-血管化-炎症”环的构建而促进子宫内膜异位症的进展。
Background: Endometriosis (EMs) is the most common gynaecological disorder with its etiology and/or pathophysiology remains enigmatic. Recent studies showed that extracellular vesicles (EVs), exosomes in particular, play a critical role in developing various clinical disorders. However, the implication of exosomes in endometriosis progression has not been well elucidated. Method: The ectopic stromal cellular exosomes (eEVs) were assessed by transwell assay, scratch tests, tube formation assay, western blot, and qRT-PCR analysis. Protein expression profiles of exosomes in endometrial tissue and vaginal discharge collected from patients with EMS and healthy donors were analysed by Mass spectrometry. siRNA interference technology was used to inhibit the expression of exosomal protein for the functional analysis in in-vivo. Finally, in-vitro experiments were performed to validate the results that we observed in EMs mouse model. Results: In vitro, we discovered that eEVs improved NSC migratory potential by upregulating MMP9 expression and activity. eEVs also aided angiogenesis and elevated the expression of inflammatory cytokines in ovarian epithelial cells, according to our findings. Moesin (MSN) levels in ESC exosomes were substantially greater than in NSC exosomes (1.22e8±5.58e6 vs. 6.605e7±4.574e6, LFQ intensity), as shown by protein mass spectrometry and bioinformatics analysis. In ectopic stromal cells, ERa receptors stimulated the RhoA/Rock-2/MSN pathway. We discovered that downregulating exosomal moesin reduced NSC migration (about 3-fold change) and MMP9 expression (about 2-fold change). On the other hand, Exomsni inhibited angiogenesis and inflammatory cytokine release. In vivo the result of immunohistochemistry and immunofluorescence demonstrated that exosomal MSN substantially modified the expression of MM9, VEGFR and p-VEGFR in polyclonal lesions. In addition, we discovered an elevation in the expression of proinflammatory factors in the surrounding tissue. Conclusion: Exosomal MSN derived from ectopic stromal cells can contribute to endometriosis progression by mediating the construction of a “migration-vascularization-inflammation” loop in the ectopic environment.
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影响因子：
4.6
作者：
Khalaj K;Ahn SH;Bidarimath M;Nasirzadeh Y;Singh SS;Fazleabas AT;Young SL;Lessey BA;Koti M;Tayade C
通讯作者：
Tayade C
影响因子：
12.4
作者：
Chen YS;Chang CW;Tsay YG;Huang LY;Wu YC;Cheng LH;Yang CC;Wu CH;Teo WH;Hung KF;Huang CY;Lee TC;Lo JF
通讯作者：
Lo JF
影响因子：
1.8
作者：
Mhawech-Fauceglia P;Wang D;Lele S;Frederick PJ;Pejovic T;Liu S
通讯作者：
Liu S
DOI：
10.4049/jimmunol.1501138
发表时间：
2015-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ahn SH;Edwards AK;Singh SS;Young SL;Lessey BA;Tayade C
通讯作者：
Tayade C
影响因子：
2.9
作者：
Filippi, Irene;Carrarelli, Patrizia;Petraglia, Felice
通讯作者：
Petraglia, Felice