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Decreased miR-325-5p Contributes to Visceral Hypersensitivity Through Post-transcriptional Upregulation of CCL2 in Rat Dorsal Root Ganglia

  • Rui Wu
  • Ping-An Zhang
  • Xuelian Liu
  • Yuan Zhou
  • Meijie Xu
  • Xinghong Jiang
  • Jun Yan
  • Guang-Yin XuEmail author
Original Article
  • 23 Downloads

Abstract

Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.

Keywords

Visceral pain Dorsal root ganglia miRNA-325-5p CCL2 Epigenetic regulation 

Notes

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81471137, 31730040, and 81771187) and from the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.

Conflict of interest

No conflicts of interest, financial or otherwise, are declared by the authors.

Supplementary material

12264_2019_372_MOESM1_ESM.tif (542 kb)
Supplementary material 1 (TIFF 542 kb)

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Rui Wu
    • 1
    • 2
  • Ping-An Zhang
    • 1
    • 2
  • Xuelian Liu
    • 2
  • Yuan Zhou
    • 2
  • Meijie Xu
    • 1
  • Xinghong Jiang
    • 2
  • Jun Yan
    • 3
  • Guang-Yin Xu
    • 1
    • 2
    Email author
  1. 1.Center for Translational MedicineAffiliated Zhangjiagang Hospital of Soochow UniversityZhangjiagangChina
  2. 2.Department of Physiology and Neurobiology, Institute of NeuroscienceSoochow UniversitySuzhouChina
  3. 3.The Second Affiliated of Hospital Soochow UniversitySuzhouChina

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