Deficiency of MIF Accentuates Overloaded Compression-Induced Nucleus Pulposus Cell Oxidative Damage via Depressing Mitophagy.
Deficiency of MIF Accentuates Overloaded Compression-Induced Nucleus Pulposus Cell Oxidative Damage via Depressing Mitophagy.
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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
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发表时间：
2021
影响因子：
--
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Wang Y;Hu Y;Wang H;Liu N;Luo L;Zhao C;Zhou D;Tong H;Li P;Zhou Q
已有的研究证明，机械压缩载荷对椎间盘（IVD）的生物学行为有多种影响。然而，这一过程的调控机制尚不清楚。本研究的目的是探讨髓核细胞在压力相关的生物学变化的潜在生物调节因子和信号通路。应用基于TMT-的定量蛋白质组学方法，分析了非压缩、低压缩（LC）和高压缩（HC）载荷下培养的不同组NP细胞之间差异表达的蛋白质（DEPs）和信号通路。通过蛋白质组学预测了8种在不同压力负荷下NP细胞存活的潜在保护性生物调节剂，其中巨噬细胞移动抑制因子（MIF）和氧化应激相关途径被选择用于进一步评估，因为其在调节软骨终板-（CEP-）衍生细胞的命运方面具有相似的功能。我们发现，MIF的缺乏加重了ROS的积累，线粒体功能障碍，和超负荷机械压力下的NP细胞衰老。这一过程的分子机制可能与MIF对线粒体自噬的调节作用有关。我们的研究结果提供了一个更好的理解的调节作用，机械压缩的细胞命运的承诺和基质代谢的NP，和潜在的策略，通过使用MIF调节剂治疗椎间盘退行性疾病。
Established studies proved that mechanical compression loading had multiple effects on the biological behavior of the intervertebral disc (IVD). However, the regulating mechanism involved in this process remains unclear. The current study is aimed at exploring the potential bioregulators and signaling pathways involved in the compression-associated biological changes of nucleus pulposus (NP) cells. Tandem mass tag- (TMT-) based quantitative proteomics was exerted to analyze the differentially expressed proteins (DEPs) and signal pathways among the different groups of NP cells cultured under noncompression, low-compression (LC), and high-compression (HC) loading. Eight potential protective bioregulators for the NP cell survival under different compression loading were predicted by the proteomics, among which macrophage migration inhibitory factor (MIF) and oxidative stress-related pathways were selected for further evaluation, due to its similar function in regulating the fate of the cartilage endplate- (CEP-) derived cells. We found that deficiency of MIF accentuates the accumulation of ROS, mitochondrial dysfunction, and senescence of NP cells under overloaded mechanical compression. The potential molecular mechanism involved in this process is related to the mitophagy regulating role of MIF. Our findings provide a better understanding of the regulatory role of mechanical compression on the cellular fate commitment and matrix metabolism of NP, and the potential strategies for treating disc degenerative diseases via using MIF-regulating agents.
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影响因子：
4.9
作者：
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DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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