Wnt5a修饰骨髓间充质干细胞介导MAPK/JNK与Notch信号通路Cross-Talk促进脊髓损伤修复作用机制及补肾活血法的干预研究

批准号:
82004384
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
李兴
依托单位:
学科分类:
中医骨伤科学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
李兴
国基评审专家1V1指导 中标率高出同行96.8%
结合最新热点,提供专业选题建议
深度指导申报书撰写,确保创新可行
指导项目中标800+,快速提高中标率
微信扫码咨询
中文摘要
神经分化率低下是骨髓间充质干细胞(BMSCs)移植治疗脊髓损伤(SCI)面临的重要问题,因此,提高BMSCs定向神经分化,对SCI修复至关重要。既往研究已证实MAPK/JNK是BMSCs促神经分化经典信号通路,而Notch是抑制信号通路。近期我们预实验发现Wnt5a具有激活MAPK/JNK和抑制Notch信号通路的双重作用,过表达Wnt5a的BMSCs具有高效的神经分化能力;而补肾活血方可显著上调Wnt5a表达。由此我们提出假说:Wnt5a通过激活MAPK/JNK通路、同时抑制Notch信号通路,获得高效BMSCs定向神经分化趋势;另一方面补肾活血方通过体内上调Wnt5a表达,进一步提高BMSCs神经分化率,进而恢复神经功能,重建神经回路,达到修复SCI目的。本课题采用体外-体内、分子-细胞-整体水平,从基因表达、组织学及动物形态学三个层次证明该假设,为高效治疗SCI提供新靶标和思路。
英文摘要
BMSCs transplantation has always been faced with the problem of low neuron differentiation rate in vivo. Therefore, improving the directional neuronal differentiation rate of BMSCs play an important role in the treatment with SCI. Previous studies reported that MAPK/JNK was a classic signaling pathway for BMSCs to promote neural differentiation, and Notch was a signaling pathway for BMSCs to inhibit neural differentiation. Recently, our results showed that Wnt5a had the dual effects of activating the MAPK/JNK pathway and inhibiting the Notch signaling pathway. Furthermore, We also found that a stronger ability was measured under the Wnt5a-overexpressed BMSCs to direct neural differentiation, and Bushen Huoxue decoction can significantly increase Wnt5a expression. Therefore, we hypothesize that Wnt5a-overexpressed BMSCs has a better ability to direct neuronal differentiation by activating the MAPK/JNK signaling pathway and inhibiting the Notch signaling pathway. After transplanting Wnt5a-overexpressed BMSCs into spinal cord injury and combining with Bushen Huoxue decoction, a higher rate of neural differentiation can be obtained, which can restore nerve function, rebuild neural circuit and improve the motor function in spinal cord injury. To prove this hypothesis, we use the different the biological technology, including the vitro-vivo, molecular-cell-integral level, gene expression, histology and animal morphology. The potential findings may provide new targets and ideas for accurate treatment with spinal cord injury.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1007/s12035-023-03754-5
发表时间:2023-11
期刊:Molecular neurobiology
影响因子:5.1
作者:Jiaxian Weng;Le Wang;Kai Wang;Haitao Su;Dan Luo;Haimei Yang;Yaqian Wen;Qiduan Wu;Xing Li
通讯作者:Jiaxian Weng;Le Wang;Kai Wang;Haitao Su;Dan Luo;Haimei Yang;Yaqian Wen;Qiduan Wu;Xing Li
DOI:10.3969/j.issn.1001-1528.2023.08.011
发表时间:2023
期刊:中成药
影响因子:--
作者:翁家贤;梁超伦;肖方骏;杨海梅;曾秀云;梁家畅;王凯;邓健平;文雅倩;王文;罗丹;李兴
通讯作者:李兴
DOI:10.1007/s12035-023-03702-3
发表时间:2023-10
期刊:Molecular Neurobiology
影响因子:5.1
作者:Zhen Li;Haitao Su;Guandai Lin;Kai Wang;Yongming Huang;Yaqian Wen;Dan Luo;Yu Hou;Xuewei Cao;Jiaxian Weng;Dingkun Lin;Le Wang;Xing Li
通讯作者:Zhen Li;Haitao Su;Guandai Lin;Kai Wang;Yongming Huang;Yaqian Wen;Dan Luo;Yu Hou;Xuewei Cao;Jiaxian Weng;Dingkun Lin;Le Wang;Xing Li
BMSCs外泌体转运Wnt5a促进神经干细胞分化修复脊髓损伤作用机制及补肾活血方的干预研究
- 批准号:--
- 项目类别:省市级项目
- 资助金额:30.0万元
- 批准年份:2024
- 负责人:李兴
- 依托单位:
牛黄熊去氧胆酸(TUDCA)靶向 Keap1-Nrf2-NQO1信号轴介导氧化应激调控骨髓间质干细胞(BMSCs)神经分化促脊髓损伤修复作用机制研究
- 批准号:n/a
- 项目类别:省市级项目
- 资助金额:10.0万元
- 批准年份:2022
- 负责人:李兴
- 依托单位:
补肾活血方介导 CircRNAs“sponge”靶向MMP- 13调控骨关节炎软骨退变的干预作用研究
- 批准号:2020A151501919
- 项目类别:省市级项目
- 资助金额:10.0万元
- 批准年份:2020
- 负责人:李兴
- 依托单位:
国内基金
海外基金
