Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis
Nerve injury induces profound and complex changes at molecular and cellular levels, leading to axonal self-destruction as well as immune and inflammatory responses that may further promote neurodegeneration. To better understand how neural injury changes the proteome within the injured nerve, we set...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:f880b7d2f1bc4937b30d7fbcc3b365b62021-11-12T07:13:40ZQuantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis1662-509910.3389/fnmol.2021.777621https://doaj.org/article/f880b7d2f1bc4937b30d7fbcc3b365b62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnmol.2021.777621/fullhttps://doaj.org/toc/1662-5099Nerve injury induces profound and complex changes at molecular and cellular levels, leading to axonal self-destruction as well as immune and inflammatory responses that may further promote neurodegeneration. To better understand how neural injury changes the proteome within the injured nerve, we set up a mouse model of sciatic nerve injury (SNI) and conducted an unbiased, quantitative proteomic study followed by biochemical assays to confirm some of the changed proteins. Among them, the protein levels of ADP-dependent glucokinase (ADPGK) were significantly increased in the injured sciatic nerve. Further examination indicated that ADPGK was specifically expressed and upregulated in macrophages but not neurons or Schwann cells upon injury. Furthermore, culturing immortalized bone marrow-derived macrophages (iBMDMs) in vitro with the conditioned media from transected axons of mouse dorsal root ganglion (DRG) neurons induced ADPGK upregulation in iBMDMs, suggesting that injured axons could promote ADPGK expression in macrophages non-cell autonomously. Finally, we showed that overexpression of ADPGK per se did not activate macrophages but promoted the phagocytotic activity of lipopolysaccharides (LPS)-treated macrophages. Together, this proteomic analysis reveals interesting changes of many proteins within the injured nerve and our data identify ADPGK as an important in vivo booster of injury-induced macrophage phagocytosis.Kai ZhangKai ZhangQingyao WangQingyao WangYiyao LiangYu YanYu YanHaiqiong WangHaiqiong WangXu CaoXu CaoBing ShanYaoyang ZhangYaoyang ZhangAng LiAng LiAng LiAng LiYanshan FangYanshan FangFrontiers Media S.A.articleperipheral nerve injuryaxon degenerationmacrophageneuroimmuneproteomicsNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Molecular Neuroscience, Vol 14 (2021) |
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| topic |
peripheral nerve injury axon degeneration macrophage neuroimmune proteomics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
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peripheral nerve injury axon degeneration macrophage neuroimmune proteomics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Kai Zhang Kai Zhang Qingyao Wang Qingyao Wang Yiyao Liang Yu Yan Yu Yan Haiqiong Wang Haiqiong Wang Xu Cao Xu Cao Bing Shan Yaoyang Zhang Yaoyang Zhang Ang Li Ang Li Ang Li Ang Li Yanshan Fang Yanshan Fang Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis |
| description |
Nerve injury induces profound and complex changes at molecular and cellular levels, leading to axonal self-destruction as well as immune and inflammatory responses that may further promote neurodegeneration. To better understand how neural injury changes the proteome within the injured nerve, we set up a mouse model of sciatic nerve injury (SNI) and conducted an unbiased, quantitative proteomic study followed by biochemical assays to confirm some of the changed proteins. Among them, the protein levels of ADP-dependent glucokinase (ADPGK) were significantly increased in the injured sciatic nerve. Further examination indicated that ADPGK was specifically expressed and upregulated in macrophages but not neurons or Schwann cells upon injury. Furthermore, culturing immortalized bone marrow-derived macrophages (iBMDMs) in vitro with the conditioned media from transected axons of mouse dorsal root ganglion (DRG) neurons induced ADPGK upregulation in iBMDMs, suggesting that injured axons could promote ADPGK expression in macrophages non-cell autonomously. Finally, we showed that overexpression of ADPGK per se did not activate macrophages but promoted the phagocytotic activity of lipopolysaccharides (LPS)-treated macrophages. Together, this proteomic analysis reveals interesting changes of many proteins within the injured nerve and our data identify ADPGK as an important in vivo booster of injury-induced macrophage phagocytosis. |
| format |
article |
| author |
Kai Zhang Kai Zhang Qingyao Wang Qingyao Wang Yiyao Liang Yu Yan Yu Yan Haiqiong Wang Haiqiong Wang Xu Cao Xu Cao Bing Shan Yaoyang Zhang Yaoyang Zhang Ang Li Ang Li Ang Li Ang Li Yanshan Fang Yanshan Fang |
| author_facet |
Kai Zhang Kai Zhang Qingyao Wang Qingyao Wang Yiyao Liang Yu Yan Yu Yan Haiqiong Wang Haiqiong Wang Xu Cao Xu Cao Bing Shan Yaoyang Zhang Yaoyang Zhang Ang Li Ang Li Ang Li Ang Li Yanshan Fang Yanshan Fang |
| author_sort |
Kai Zhang |
| title |
Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis |
| title_short |
Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis |
| title_full |
Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis |
| title_fullStr |
Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis |
| title_full_unstemmed |
Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis |
| title_sort |
quantitative proteomic analysis of mouse sciatic nerve reveals post-injury upregulation of adp-dependent glucokinase promoting macrophage phagocytosis |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/f880b7d2f1bc4937b30d7fbcc3b365b6 |
| work_keys_str_mv |
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