缺氧诱导的 Semaphorin 3A 通过调节巨噬细胞极化促进子宫内膜异位症的发展。
Hypoxia-induced Semaphorin 3A promotes the development of endometriosis through regulating macrophage polarization.
发表日期：2024 Jul 01
作者：
Ruyu Yang, Fan Yang, Yajing Wei, Biqi Huang, Tiefeng Cao, Hao Tan, Duo Liu, Qiuyu Zou, Jinjuan Wen, Lei Wen, Xi Lu, Changyang Yu, Heng Cai, Xiaofei Xie, Shaoru Jiang, Shuzhong Yao, Yanchun Liang
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要：
Semaphorin 3A (Sema3A) 是神经引导因子家族的一员，以诱导神经细胞生长锥塌陷和调节神经重新分布而闻名。它还被认为是一种免疫调节和肿瘤促进因子。我们前期的研究表明Sema3A参与了子宫内膜异位症交感神经支配和神经病理性疼痛的调节。然而，Sema3A在子宫内膜异位症发生发展中的作用及其潜在的上游因子仍不清楚。组织学实验检测Sema3A、缺氧诱导因子1α（HIF-1α）的表达以及巨噬细胞的分布。通过细胞实验探讨Sema3A对子宫内膜基质细胞（ESC）增殖和迁移的影响，并证实HIF-1α对Sema3A的调节作用。通过体内实验探讨Sema3A在子宫内膜异位症发生发展中的作用。Sema3A在子宫内膜异位病灶中高表达，能够增强ESCs的增殖和迁移能力。在子宫内膜异位病变中发现异常的巨噬细胞分布。 Sema3A还促进单核细胞分化为抗炎巨噬细胞，从而间接介导ESC的增殖和迁移。缺氧微环境通过 HIF-1α 诱导 ESC 中 Sema3A mRNA 和蛋白表达。在小鼠模型中，给予Sema3A可促进子宫内膜异位症的发生。Sema3A受HIF-1α调节，是子宫内膜异位症发生的促进因子。靶向 Sema3A 可能是控制子宫内膜异位病变的潜在治疗策略。版权所有 © 2024。由 Elsevier B.V. 出版。
Semaphorin 3A (Sema3A) is a member of neural guidance factor family well-known for inducing the collapse of nerve cell growth cone and regulating nerve redistribution. It also has been characterized as an immunoregulatory and tumor promoting factor. Our previous study showed that Sema3A was involved in the regulation of sympathetic innervation and neuropathic pain of endometriosis. Nevertheless, the role of Sema3A in the development of endometriosis and its potential upstreaming factor are still not clear.Histology experiments were carried to detect the expression of Sema3A, hypoxia -inducible factor 1α (HIF-1α) and the distribution of macrophages. Cell experiments were used to explore the effect of Sema3A on the proliferation and migration of endometrial stromal cells (ESCs) and to confirm the regulatory action of HIF-1α on Sema3A. In vivo experiments were carried out to explore the role of Sema3A on the development of endometriosis.Sema3A was highly expressed in endometriotic lesions and could enhanced the proliferation and migration abilities of ESCs. Aberrant macrophage distribution was found in endometriotic lesions. Sema3A also promoted the differentiation of monocytes into anti-inflammatory macrophages, so indirectly mediating the proliferation and migration of ESCs. Hypoxic microenvironment induced Sema3A mRNA and protein expression in ESCs via HIF-1α. Administration of Sema3A promoted the development of endometriosis in a mouse model.Sema3A, which is regulated by HIF-1α, is a promoting factor for the development of endometriosis. Targeting Sema3A may be a potential treatment strategy to control endometriotic lesions.Copyright © 2024. Published by Elsevier B.V.