Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons

Peripheral nerve injury increased the expression of the DNA methyltransferase 3A (Dnmt3a) mRNA and its encoding Dnmt3a protein in injured dorsal root ganglia (DRG). This increase is considered as an endogenous instigator in neuropathic pain genesis through epigenetic silencing of pain-associated gen...

Full description

Bibliographic Details
Main Authors: Bo Xu, Jing Cao, Jun Zhang, Shushan Jia, Shaogen Wu, Kai Mo, Guihua Wei, Lingli Liang, Xuerong Miao, Alex Bekker, Yuan-Xiang Tao
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-11-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fnmol.2017.00350/full
id doaj-e02c2913179d49c09e32008d24e49d4f
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Bo Xu
Bo Xu
Jing Cao
Jing Cao
Jun Zhang
Jun Zhang
Shushan Jia
Shushan Jia
Shaogen Wu
Kai Mo
Guihua Wei
Lingli Liang
Xuerong Miao
Alex Bekker
Yuan-Xiang Tao
Yuan-Xiang Tao
Yuan-Xiang Tao
spellingShingle Bo Xu
Bo Xu
Jing Cao
Jing Cao
Jun Zhang
Jun Zhang
Shushan Jia
Shushan Jia
Shaogen Wu
Kai Mo
Guihua Wei
Lingli Liang
Xuerong Miao
Alex Bekker
Yuan-Xiang Tao
Yuan-Xiang Tao
Yuan-Xiang Tao
Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons
Frontiers in Molecular Neuroscience
miR-143
Dnmt3a
Oprm1
dorsal root ganglion
neuropathic pain
author_facet Bo Xu
Bo Xu
Jing Cao
Jing Cao
Jun Zhang
Jun Zhang
Shushan Jia
Shushan Jia
Shaogen Wu
Kai Mo
Guihua Wei
Lingli Liang
Xuerong Miao
Alex Bekker
Yuan-Xiang Tao
Yuan-Xiang Tao
Yuan-Xiang Tao
author_sort Bo Xu
title Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons
title_short Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons
title_full Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons
title_fullStr Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons
title_full_unstemmed Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons
title_sort role of microrna-143 in nerve injury-induced upregulation of dnmt3a expression in primary sensory neurons
publisher Frontiers Media S.A.
series Frontiers in Molecular Neuroscience
issn 1662-5099
publishDate 2017-11-01
description Peripheral nerve injury increased the expression of the DNA methyltransferase 3A (Dnmt3a) mRNA and its encoding Dnmt3a protein in injured dorsal root ganglia (DRG). This increase is considered as an endogenous instigator in neuropathic pain genesis through epigenetic silencing of pain-associated genes (such as Oprm1) in injured DRG. However, how DRG DNMT3a is increased following peripheral nerve injury is still elusive. We reported here that peripheral nerve injury caused by the fifth spinal nerve ligation (SNL) downregulated microRNA (miR)-143 expression in injured DRG. This downregulation was required for SNL-induced DRG Dnmt3a increase as rescuing miR-143 downregulation through microinjection of miR-143 mimics into injured DRG blocked the SNL-induced increase in Dnmt3a and restored the SNL-induced decreases in Oprm1 mRNA and its encoding mu opioid receptor (MOR) in injured DRG, impaired spinal cord central sensitization and neuropathic pain, and improved morphine analgesic effects following SNL. Mimicking SNL-induced DRG miR-143 downregulation through DRG microinjection of miR143 inhibitors in naive rats increased the expression of Dnmt3a and reduced the expression of Oprm1 mRNA and MOR in injected DRG and produced neuropathic pain-like symptoms. These findings suggest that miR-143 is a negative regulator in Dnmt3a expression in the DRG under neuropathic pain conditions and may be a potential target for therapeutic management of neuropathic pain.
topic miR-143
Dnmt3a
Oprm1
dorsal root ganglion
neuropathic pain
url http://journal.frontiersin.org/article/10.3389/fnmol.2017.00350/full
work_keys_str_mv AT boxu roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT boxu roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT jingcao roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT jingcao roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT junzhang roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT junzhang roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT shushanjia roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT shushanjia roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT shaogenwu roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT kaimo roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT guihuawei roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT lingliliang roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT xuerongmiao roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT alexbekker roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT yuanxiangtao roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT yuanxiangtao roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
AT yuanxiangtao roleofmicrorna143innerveinjuryinducedupregulationofdnmt3aexpressioninprimarysensoryneurons
_version_ 1725996248998084608
spelling doaj-e02c2913179d49c09e32008d24e49d4f2020-11-24T21:22:21ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-11-011010.3389/fnmol.2017.00350285485Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory NeuronsBo Xu0Bo Xu1Jing Cao2Jing Cao3Jun Zhang4Jun Zhang5Shushan Jia6Shushan Jia7Shaogen Wu8Kai Mo9Guihua Wei10Lingli Liang11Xuerong Miao12Alex Bekker13Yuan-Xiang Tao14Yuan-Xiang Tao15Yuan-Xiang Tao16Department of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, General Hospital of Guangzhou Military Command, Guangzhou, ChinaDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesNeuroscience Research Institute, College of Basic Medicine, Zhengzhou University, Zhengzhou, ChinaDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, Union Medical Center, Tianjin, ChinaDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, ChinaDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesDepartment of Anesthesiology, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesNeuroscience Research Institute, College of Basic Medicine, Zhengzhou University, Zhengzhou, ChinaDepartments of Cell Biology & Molecular Medicine and Physiology, Pharmacology & Neuroscience, Rutgers New Jersey Medical School, The State University of New Jersey, Newark, NJ, United StatesPeripheral nerve injury increased the expression of the DNA methyltransferase 3A (Dnmt3a) mRNA and its encoding Dnmt3a protein in injured dorsal root ganglia (DRG). This increase is considered as an endogenous instigator in neuropathic pain genesis through epigenetic silencing of pain-associated genes (such as Oprm1) in injured DRG. However, how DRG DNMT3a is increased following peripheral nerve injury is still elusive. We reported here that peripheral nerve injury caused by the fifth spinal nerve ligation (SNL) downregulated microRNA (miR)-143 expression in injured DRG. This downregulation was required for SNL-induced DRG Dnmt3a increase as rescuing miR-143 downregulation through microinjection of miR-143 mimics into injured DRG blocked the SNL-induced increase in Dnmt3a and restored the SNL-induced decreases in Oprm1 mRNA and its encoding mu opioid receptor (MOR) in injured DRG, impaired spinal cord central sensitization and neuropathic pain, and improved morphine analgesic effects following SNL. Mimicking SNL-induced DRG miR-143 downregulation through DRG microinjection of miR143 inhibitors in naive rats increased the expression of Dnmt3a and reduced the expression of Oprm1 mRNA and MOR in injected DRG and produced neuropathic pain-like symptoms. These findings suggest that miR-143 is a negative regulator in Dnmt3a expression in the DRG under neuropathic pain conditions and may be a potential target for therapeutic management of neuropathic pain.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00350/fullmiR-143Dnmt3aOprm1dorsal root ganglionneuropathic pain