Netrin-1促进子宫内膜异位症发生发展及其介导疼痛敏化的作用机制研究

批准号:
81974225
项目类别:
面上项目
资助金额:
53.0 万元
负责人:
张信美
依托单位:
学科分类:
子宫内膜异位症与子宫腺肌症
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
张信美
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中文摘要
子宫内膜异位症(内异症)虽为一种良性妇科疾病,却有增生、浸润、远处转移及复发等恶性肿瘤学行为。Netrin-1有抗细胞凋亡和促进肿瘤细胞浸润转移的作用,而在内异症中是否抗凋亡和介导子宫内膜细胞的浸润迁移仍然不明。我们发现Netrin-1在内异症病灶中过表达,且Netrin-1水平在患者血清中显著增高,提示Netrin-1介导内异症的发生发展,而具体机制需要进一步研究。此外,Netrin-1还促进新生血管形成及调控神经轴突的导向和生长,血管与神经往往伴行。内异症病灶神经纤维分布密度与患者疼痛程度呈正相关。通过前期实验我们还发现内异症病灶及血清中Netrin-1表达水平与患者疼痛呈正相关,然而,Netrin-1是否介导内异症新生血管形成及神经纤维的异常生长而导致疼痛仍然不清楚。通过本课题将明确Netrin-1调控内异症发生发展及介导疼痛敏化的作用机制,为内异症的治疗提供新依据和新靶点。
英文摘要
Endometriosis is a common benign gynecological disease, but it has malignant behaviors such as hyperplasia, invasion, metastasis and recurrence. Netrin-1 can inhibit apoptosis and promote invasion and metastasis of tumor cells, but whether Netrin-1 can inhibit apoptosis and mediate invasion and migration of endometrial cells in endometriosis is still unknown. Preliminarily, we found that Netrin-1 was over-expressed in endometriotic lesions and that the levels of Netrin-1 in serum were significantly higher in women with endometriosis than those in women without endometriosis, suggesting that Netrin-1 mediates the occurrence and development of endometriosis, and the specific mechanism needs further study. Furthermore, Netrin-1 also promotes angiogenesis and regulates the direction and growth of nerve axons, and blood vessels and nerves often go hand in hand (called angioneurogenesis). We also found that the expression levels of Netrin-1 in ectopic endometrium were positively correlated with endometriosis pain and that serum Netrin-1 levels in endometriosis patients with pain were significantly higher than those in endometriosis patients without pain. As for endometriosis patients, the density of nerve fibers in endometriotic lesions was associated with the severity of pain symptoms. However, it remains unclear whether Netrin-1 mediates neovascularization and abnormal growth of nerve fibers, leading to pain in endometriosis. Therefore, this project will clarify the role and mechanisms of Netrin-1 regulating the occurrence and development of endometriosis and mediating pain sensitization, which would provide a new theoretical basis and therapeutic target for the treatment of endometriosis.
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DOI:DOI: 10.3389/fimmu.2021.749979
发表时间:2021
期刊:Frontiers in Immunology
影响因子:7.3
作者:Xinyue Guo Gen;Xinxin Xu;Tiantian Li;Qin Yu;Jianzhang Wang;Yichen Chen;Shaojie Ding;Libo Zhu;Gen Zou;Xinmei Zhang
通讯作者:Xinmei Zhang
Macrophage-derived netrin-1 is critical for neuroangiogenesis in endometriosis
巨噬细胞衍生的 netrin-1 对于子宫内膜异位症的神经血管生成至关重要
DOI:10.1016/j.ijbiomac.2020.01.130
发表时间:2020-04-01
期刊:INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
影响因子:8.2
作者:Guo, Xinyue;Ding, Shaojie;Zhang, Xinmei
通讯作者:Zhang, Xinmei
Efficacy of the levonorgestrel-releasing intrauterine device is associated with different subtypes of adenomyosis: a retrospective study.
左炔诺孕酮宫内节育器的疗效与不同亚型的子宫腺肌病相关:一项回顾性研究
DOI:10.21037/atm-20-3420
发表时间:2020-11
期刊:Annals of translational medicine
影响因子:--
作者:Chen S;Wang J;Sun W;Zhu L;He J;Zhang X
通讯作者:Zhang X
DOI:10.1001/jamanetworkopen.2023.17860
发表时间:2023-06-01
期刊:JAMA network open
影响因子:13.8
作者:
通讯作者:
DOI:10.7150/ijbs.72707
发表时间:2022
期刊:INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
影响因子:9.2
作者:Liu, Yuanmeng;Wang, Jianzhang;Zhang, Xinmei
通讯作者:Zhang, Xinmei
MRGPRX2/B2调控肥大细胞活化介导子宫内膜异位症疼痛敏化的分子机制研究
- 批准号:82171636
- 项目类别:面上项目
- 资助金额:55万元
- 批准年份:2021
- 负责人:张信美
- 依托单位:
RON介导的上皮-间质转换在子宫内膜异位症发生发展中的作用机制研究
- 批准号:81671429
- 项目类别:面上项目
- 资助金额:57.0万元
- 批准年份:2016
- 负责人:张信美
- 依托单位:
ATP和P2X3受体参与雌激素调节子宫内膜异位症疼痛信号转导通路的作用及机制研究
- 批准号:81471433
- 项目类别:面上项目
- 资助金额:74.0万元
- 批准年份:2014
- 负责人:张信美
- 依托单位:
MAPK/CREB信号转导通路与子宫内膜异位症疼痛敏化调控机制研究
- 批准号:81270672
- 项目类别:面上项目
- 资助金额:70.0万元
- 批准年份:2012
- 负责人:张信美
- 依托单位:
糖脂纳米载体介导PEDF治疗子宫内膜异位症的疗效及其机制研究
- 批准号:81070468
- 项目类别:面上项目
- 资助金额:32.0万元
- 批准年份:2010
- 负责人:张信美
- 依托单位:
雌激素调控子宫内膜异位症病灶神经产生致疼痛的机理研究
- 批准号:30872754
- 项目类别:面上项目
- 资助金额:8.0万元
- 批准年份:2008
- 负责人:张信美
- 依托单位:
国内基金
海外基金
