共 48 条
Nogo-A promotes inflammatory heat hyperalgesia by maintaining TRPV-1 function in the rat dorsal root ganglion neuron
被引:17
作者:
Hu, Fang
[1
,2
]
Liu, Huai-Cun
[3
]
Su, Dong-Qiang
[3
]
Chen, Hai-Jing
[1
]
Chan, Sun-On
[4
]
Wang, Yun
[1
,5
]
Wang, Jun
[3
]
机构:
[1] Peking Univ, Hlth Sci Ctr,Dept Neurobiol, Natl Hlth Commiss,Neurosci Res Inst, Key Lab Neurosci,Minist Educ & Neurosci, Beijing, Peoples R China
[2] Qingdao Univ, Sch Pharm, Dept Pharmacol, Qingdao, Peoples R China
[3] Peking Univ, Sch Basic Med Sci, Dept Anat & Histol, 38 Xueyuan Rd, Beijing 100083, Peoples R China
[4] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China
[5] Peking Univ, McGovern Inst Brain Res, Peking Univ Int Data Grp PKU IDG, Beijing, Peoples R China
基金:
中国国家自然科学基金;
北京市自然科学基金;
关键词:
RTN4A;
inflammatory pain;
cytoskeleton;
PRIMARY SENSORY NEURONS;
NEURITE OUTGROWTH INHIBITOR;
MYELIN-ASSOCIATED INHIBITOR;
AXON REGENERATION;
MESSENGER-RNA;
MICE LACKING;
SPINAL-CORD;
RECEPTOR;
PROTEIN;
KINASE;
D O I:
10.1096/fj.201800382RR
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Nogo-A is a key inhibitory molecule of axon regeneration in oligodendrocytes. However, little is known about its role in adult neurons. In this study, we showed an important function of Nogo-A on regulation of inflammatory pain in dorsal root ganglion (DRG) neurons. In adult rats with complete Freund's adjuvant (CFA) hind paw inflammation, DRG neurons showed a significant increase in Nogo-A expression. Disruption of Nogo-A signaling with Nogo-66 receptor antagonist peptide, Nogo-A blocking antibody, Nogo-A short hairpin RNA, or Nogo-A gene knockout attenuated CFA-induced inflammatory heat hyperalgesia. Moreover, disruption of Nogo-A signaling suppressed the function and expression in DRG neurons of the transient receptor potential vanilloid subfamily member (TRPV)-1 channel, which is known to be the endogenous transducer of noxious heat during inflammation. These effects were accompanied with a reduction in LIM domain kinase (LIMK)/cofilin phosphorylation and actin polymerization. Similar disruption of actin filament architecture by direct action of Latrunculin A reduced the TRPV-1 activity and up-regulation of TRPV-1 protein caused by CFA. We conclude that Nogo-A plays an essential role in the development of inflammatory heat hyperalgesia, partly through maintaining TRPV-1 function via activation of the LIMK/cofilin pathway, which regulates actin filament dynamics. These findings support a therapeutic potential of modulating Nogo-A signaling in pain management.Hu, F., Liu, H.-C., Su, D.-Q., Chen, H.-J., Chan, S.-O., Wang, Y., Wang, J. Nogo-A promotes inflammatory heat hyperalgesia by maintaining TRPV-1 function in the rat dorsal root ganglion neuron.
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页码:668 / 682
页数:15
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