miR‐34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway and induces the release of CGRP via inhibition of SIRT1 in rat trigeminal ganglion neurons

Autor: Sheng-Dong He, Hui Zhang, Dan-Dan Zong, Xue-Mei Zhang, Feng-Zheng Zhang, Hua Jiang, Xiao-Ying Ji
Rok vydání: 2020
Předmět:
0301 basic medicine
Interleukin-1beta
Apoptosis
Pathogenesis
Trigeminal ganglion
0302 clinical medicine
Sirtuin 1
migraine
CGRP
Prostaglandin E2
Research Articles
Cells
Cultured
Neurons
Chemistry
Up-Regulation
Trigeminal Ganglion
030220 oncology & carcinogenesis
PGE2
medicine.symptom
COX2
Research Article
Signal Transduction
medicine.drug
medicine.medical_specialty
Calcitonin Gene-Related Peptide
Migraine Disorders
Primary Cell Culture
Down-Regulation
Neuropeptide
Inflammation
Calcitonin gene-related peptide
Dinoprostone
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
SIRT1
Internal medicine
medicine
Animals
Humans
Gene silencing
Trigeminal nerve
miR‐34a‐5p
Rats
Disease Models
Animal
MicroRNAs
030104 developmental biology
Endocrinology
Animals
Newborn
Cyclooxygenase 2
Zdroj: FEBS Open Bio
ISSN: 2211-5463
DOI: 10.1002/2211-5463.13027
Popis: miR‐34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway and induces apoptosis and the release of calcitonin gene‐related peptide via inhibition of SIRT1 expression in trigeminal ganglion neurons. This suggests that miR‐34a‐5p may have potential for development into a therapeutic target for the treatment of migraine.
Migraine is a debilitating neurological condition, with a global prevalence rate of 10.68% in men and 18.79% in women. Elucidation of the molecular mechanisms underlying migraines is of great importance for improving the quality of life of patients. The release of the neuropeptide calcitonin gene‐related peptide (CGRP) from trigeminal nerve terminals is involved in the pathogenesis of migraine. Recent studies have shown that up‐regulation of miR‐34a‐5p expression is associated with acute migraine attacks. Here, we investigated whether alteration of the expression of miR‐34a‐5p induces the release of the vasoactive peptide CGRP. We isolated primary rat trigeminal ganglion neurons and performed gain‐ and loss‐of‐function assays to alter the expression level of miR‐34a‐5p. Down‐regulation of miR‐34a‐5p inhibited the expression of interleukin‐1β (IL‐1β)/cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2), decreased IL‐1β, PGE2 and CGRP release, and up‐regulated the expression of silencing information regulator 1 (SIRT1) in trigeminal ganglion, whereas overexpression of miR‐34a‐5p enhanced the expression of IL‐1β/COX2/PGE2, increased the release of IL‐1β, PGE2 and CGRP, and decreased the expression of SIRT1 in trigeminal ganglion. In addition, overexpression of miR‐34a‐5p induced apoptosis in primary rat trigeminal neurons. In summary, these findings suggest that miR‐34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway, induces apoptosis and enhances release of CGRP via inhibition of SIRT1 expression in trigeminal ganglion neurons; thus, miR‐34a‐5p may have potential as a therapeutic target for the treatment of migraine.
Databáze: OpenAIRE
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