CD146对子宫内膜异位症新生血管形成的潜在作用

The Potential Role of CD146 in Neovascularization of Endometriosis

子宫内膜异位症(endometriosis,EMs)已经成为全球瞩目的公共卫生问题,是严重影响育龄期妇女生活质量的疾病之一。新生血管形成是EMs病灶形成的必备条件。CD146不仅参与炎症调节,近年研究发现CD146还参与肿瘤的新生血管形成。有研究表明,EMs患者异位病灶的CD146较在位内膜中表达升高,提示CD146可能参与EMs的发生发展,但确切的机制尚不明确。就新生血管形成方面,CD146的异常表达对EMs的发生发展可能发挥重要作用。表达在间充质干细胞(MSCs)表面的CD146可以促进MSCs向血管平滑肌细胞(VSMC)系分化、可溶性CD146(sCD146)与血管抑素结合蛋白结合上调磷酸化黏着斑激酶(p-FAK),磷酸化蛋白激酶B(p-AKT),磷酸化应激活化蛋白激酶(pJNK)促进内皮细胞的增殖和迁移,CD146亦可与血管内皮生长因子受体2(VEGFR-2)形成共受体增强血管内皮生长因子(VEGF)激活的信号转导,促进新生血管形成;CD146作为成纤维细胞生长因子(FGF)受体促进内皮细胞的增殖、迁移;亦可与血小板衍生生长因子受体β(PDGFR-β)形成共受体促进血管管状结构的形成。

Endometriosis(EMs) has become a global public health problem that affects about 30%-50% of childbearing age women in the world. Neonatal angiogenesis is a prerequisite for the formation of endometriosis. CD146 not only involved in inflammation regulation, recent studies have found that CD146 also involved in tumor neovascularization. Studies have shown that EMs in ectopic lesions of CD146 increased expression of healthy endometrium, suggesting that CD146 may be involved in the development of EMs, but the exact mechanism is unclear. In terms of neovascularization, abnormal expression of CD146 may play an important role in the development of EMs. Expression of CD146 on the surface of mesenchymal stem cells(MSCs) can promote the differentiation of MSCs into vascular smooth muscle cells(VSMC), sCD146 binds angiomotin in EPC and up-regulates phosphorylated focal adhesion kinase(p-FAK), phosphorylated protein kinase B(p-AKT), phosphorylated stressactivated protein kinase(p-JNK) promotes endothelial cell proliferation and migration, and can also form a co-receptor with vascular endothelial growth factor receptor-2(VEGFR-2) to enhance vascular endothelial growth factor(VEGF)-activated signal transduction to promote neovascularization. CD146 as a fibroblast growth factor(FGF) receptor to promote endothelial cell proliferation and migration; CD146 can also form a co-receptor with platelet-derived growth factor receptor-β(PDGFR-β)Receptors promote the formation of vascular tubular structures.