PMID- 35911694
OWN - NLM
STAT- MEDLINE
DCOM- 20220802
LR  - 20220804
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Involvement of Histone Lysine Crotonylation in the Regulation of 
      Nerve-Injury-Induced Neuropathic Pain.
PG  - 885685
LID - 10.3389/fimmu.2022.885685 [doi]
LID - 885685
AB  - Histone lysine crotonylation (KCR), a novel epigenetic modification, is important 
      in regulating a broad spectrum of biological processes and various diseases. 
      However, whether KCR is involved in neuropathic pain remains to be elucidated. We 
      found KCR occurs in macrophages, sensory neurons, and satellite glial cells of 
      trigeminal ganglia (TG), neurons, astrocytes, and microglia of the medulla 
      oblongata. KCR in TG was detected mainly in small and medium sensory neurons, to 
      a lesser extent in large neurons. Peripheral nerve injury elevated KCR levels in 
      macrophages in the trigeminal and dorsal root ganglia and microglia in the 
      medulla oblongata but reduced KCR levels in sensory neurons. Inhibition of 
      histone crotonyltransferases (p300) by intra-TG or intrathecal administration of 
      C646 significantly alleviated partial infraorbital nerve transection (pIONT)- or 
      spinal nerve ligation (SNL)-induced mechanical allodynia and thermal 
      hyperalgesia. Intra-TG or intrathecal administration of Crotonyl coenzyme A 
      trilithium salt to upregulate KCR dose-dependently induced mechanical allodynia 
      and thermal hyperalgesia in mice. Mechanismly, inhibition of p300 alleviated 
      pIONT-induced macrophage activation and reduced the expression of pain-related 
      inflammatory cytokines Tnfalpha, Il1beta and chemokines Ccl2 and Cxcl10. 
      Correspondingly, exogenous crotonyl-CoA induced macrophage activation and the 
      expression of Tnfalpha, Il1beta, Il6, Ccl2 and Ccl7 in TG, which C646 can repress. These 
      findings suggest that histone crotonylation might be functionally involved in 
      neuropathic pain and neuroinflammation regulation.
CI  - Copyright (c) 2022 Zou, Bai, Kong, Xu, Ding, Zhang, Dong, Ling and Jiang.
FAU - Zou, Yu
AU  - Zou Y
AD  - Pain Research Laboratory, Institute of Nautical Medicine, Nantong University, 
      Nantong, China.
FAU - Bai, Xue-Hui
AU  - Bai XH
AD  - Pain Research Laboratory, Institute of Nautical Medicine, Nantong University, 
      Nantong, China.
FAU - Kong, Ling-Chi
AU  - Kong LC
AD  - Pain Research Laboratory, Institute of Nautical Medicine, Nantong University, 
      Nantong, China.
FAU - Xu, Fei-Fei
AU  - Xu FF
AD  - Medical School of Nantong University, Nantong, China.
FAU - Ding, Ting-Yu
AU  - Ding TY
AD  - Pain Research Laboratory, Institute of Nautical Medicine, Nantong University, 
      Nantong, China.
FAU - Zhang, Peng-Fei
AU  - Zhang PF
AD  - Pain Research Laboratory, Institute of Nautical Medicine, Nantong University, 
      Nantong, China.
FAU - Dong, Fu-Lu
AU  - Dong FL
AD  - Medical School of Nantong University, Nantong, China.
FAU - Ling, Yue-Juan
AU  - Ling YJ
AD  - Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 
      Nantong, China.
FAU - Jiang, Bao-Chun
AU  - Jiang BC
AD  - Pain Research Laboratory, Institute of Nautical Medicine, Nantong University, 
      Nantong, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220714
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Histones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Histones/metabolism
MH  - *Hyperalgesia/etiology/metabolism
MH  - Lysine
MH  - Mice
MH  - *Neuralgia/etiology/metabolism
MH  - Sensory Receptor Cells/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC9329947
OTO - NOTNLM
OT  - chemokine
OT  - histone crotonylation
OT  - inflammatory cytokines
OT  - macrophage
OT  - neuropathic pain
OT  - partial infraorbital nerve transection
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/02 06:00
MHDA- 2022/08/03 06:00
PMCR- 2022/01/01
CRDT- 2022/08/01 03:50
PHST- 2022/02/28 00:00 [received]
PHST- 2022/06/22 00:00 [accepted]
PHST- 2022/08/01 03:50 [entrez]
PHST- 2022/08/02 06:00 [pubmed]
PHST- 2022/08/03 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.885685 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jul 14;13:885685. doi: 10.3389/fimmu.2022.885685. eCollection 
      2022.