期刊
FEBS OPEN BIO
卷 11, 期 1, 页码 300-311出版社
WILEY
DOI: 10.1002/2211-5463.13027
关键词
CGRP; COX2; migraine; miR‐ 34a‐ 5p; PGE2; SIRT1
资金
- National Natural Science Foundation of China [81704173]
- Major Project of Education Department in Sichuan [16ZA0191, 17ZA0446]
Studies have shown that miR-34a-5p can up-regulate the IL-1 beta/COX2/PGE2 inflammation pathway, induce apoptosis, enhance CGRP release, and thereby affect the pathogenesis of migraines.
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-1 beta (IL-1 beta)/cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2), decreased IL-1 beta, 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-1 beta/COX2/PGE2, increased the release of IL-1 beta, 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-1 beta/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.
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