AQP-3下调介导PINK1/Parkin途径线粒体自噬减退在高负荷压应力促进椎间盘退变中的作用及机制研究

批准号:
81974346
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
周强
依托单位:
学科分类:
骨、关节、软组织退行性病变
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
周强
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中文摘要
高负荷压应力可增强氧化应激损伤促进髓核细胞凋亡和衰老,是椎间盘退变的重要危险因素。线粒体自噬可减轻氧化应激损伤维持细胞稳态。既往研究提示AQP-3与椎间盘退变有关,可减轻髓核细胞凋亡和衰老样命运改变,且与线粒体自噬上游信号通路关系密切。我们前期研究发现高负荷压应力促进髓核细胞凋亡和衰老时,伴随AQP-3和PINK1/Parkin途径线粒体自噬相关分子表达下调和细胞氧化应激损伤加重。我们推测:高负荷压应力下,AQP-3下调可通过减弱PINK1/Parkin途径线粒体自噬增强氧化应激损伤,继而促进髓核细胞凋亡和衰老,加速椎间盘退变。本项目拟在体外和体内通过特异性阻断或基因过表达等技术,探讨AQP-3下调介导PINK1/Parkin途径线粒体自噬减退在高负荷压应力促进椎间盘退变中的作用及机制。本研究将有助于阐明压应力相关椎间盘退变的病理机制,为探索新的椎间盘退变防治策略提供理论依据。
英文摘要
High compressive stress can promote apoptosis- and senescence-like cellular fates of nucleus pulposus (NP) cells through enhancing oxidative stresss injury, and it is regarded as an important risk factor of intervertebral disc degeneration (IDD). Mitophagy can alleviate oxidative stress to maintain cellular homeostatsis. Previous studies have found that aquaporin-3 (AQP-3) is closely related with IDD and AQP-3 can attenuate apoptosis- and senescence-like cellular fates of NP cells, moreover, AQP-3 is closely related with the upstream signal pathways of mitophagy. Our preliminary experiments show that high compressive stress-aggravated NP cell apoptosis and senescence are accompanied with the decrease in expression of AQP-3 and the PINK1/Parkin-mediated mitophagy-related molecules, and the enhancement of oxidative stress injury. Therefore, we deduce that AQP-3 downregulation can enhance oxidative stress injury through attenuating PINK1/Parkin-mediated mitophagy, and thus promote apoptosis- and senescence-like cellular fates of nucleus pulposus (NP) cells, and ultimately accelerate disc degeneration under high compressive stress. This study will using technologies of specific intervention and gene overexpression in vitro and in vivo to investigate the role and signal transduction of AQP-3 downregulation-mediated attenuation of PINK1/Parkin-mediated mitophagy in high compressive stress-promoted disc degeneration. This study will be helpful to understand the pathogenesis of mechanical load-related disc degeneration and provide theoretical evidence for the novel prevention and therapy of disc degeneration.
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DOI:10.1155/2022/1639560
发表时间:2022
期刊:PAIN RESEARCH & MANAGEMENT
影响因子:2.9
作者:Zhang, Zetong;Zhao, Chen;Zhang, Ruijie;Wang, Yiyang;Hu, Yanzhu;Zhou, Qiang;Li, Pei
通讯作者:Li, Pei
Deficiency of MIF Accentuates Overloaded Compression-Induced Nucleus Pulposus Cell Oxidative Damage via Depressing Mitophagy.
MIF 缺乏通过抑制线粒体自噬加剧超负荷压缩诱导的髓核细胞氧化损伤
DOI:10.1155/2021/6192498
发表时间:2021
期刊:Oxidative medicine and cellular longevity
影响因子:--
作者:Wang Y;Hu Y;Wang H;Liu N;Luo L;Zhao C;Zhou D;Tong H;Li P;Zhou Q
通讯作者:Zhou Q
Hydrostatic Pressure Modulates Intervertebral Disc Cell Survival and Extracellular Matrix Homeostasis via Regulating Hippo-YAP/TAZ Pathway.
静水压通过调节 Hippo-YAP/TAZ 通路调节椎间盘细胞存活和细胞外基质稳态
DOI:10.1155/2021/5626487
发表时间:2021
期刊:Stem cells international
影响因子:4.3
作者:Wang Y;Bai B;Hu Y;Wang H;Liu N;Li Y;Li P;Zhou G;Zhou Q
通讯作者:Zhou Q
DOI:10.7150/ijbs.70903
发表时间:2022
期刊:INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
影响因子:9.2
作者:Wang, Yiyang;Wang, Haoming;Zhuo, Yunyun;Hu, Yanzhu;Li, Xiaoxiao;Xu, Yanqin;Sun, Biemin;Liu, Min;Zou, Luetao;Liu, Liehua;Luo, Lei;Zhao, Chen;Li, Pei;Zhou, Qiang
通讯作者:Zhou, Qiang
DOI:10.7150/ijms.90591
发表时间:2024
期刊:International journal of medical sciences
影响因子:3.6
作者:Zou L;Wang Y;Hu Y;Liu L;Luo L;Chen Z;Zhuo Y;Li P;Zhou Q
通讯作者:Zhou Q
钙网蛋白“反转位”介导的力—生物学信号转导在低负荷压应力促进髓核自修复中的作用及机制
- 批准号:--
- 项目类别:面上项目
- 资助金额:52万元
- 批准年份:2022
- 负责人:周强
- 依托单位:
SIRT1下调介导氧化应激损伤在高负荷压应力促进椎间盘退变中的作用及机制研究
- 批准号:81772378
- 项目类别:面上项目
- 资助金额:55.0万元
- 批准年份:2017
- 负责人:周强
- 依托单位:
国内基金
海外基金
