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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.
FEBS Open Bio. 2021 01; 11(1):300-311.FO

Abstract

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.

Authors+Show Affiliations

The Second Affiliated Hospital of Guilin Medical University, China. College of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China.College of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China.The Second Xiangya Hospital, Central South University, Changsha, China.The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.College of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China.College of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China.The Second Affiliated Hospital of Guilin Medical University, China. College of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33155431

Citation

Zhang, Hui, et al. "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." FEBS Open Bio, vol. 11, no. 1, 2021, pp. 300-311.
Zhang H, Zhang XM, Zong DD, et al. 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. FEBS Open Bio. 2021;11(1):300-311.
Zhang, H., Zhang, X. M., Zong, D. D., Ji, X. Y., Jiang, H., Zhang, F. Z., & He, S. D. (2021). 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. FEBS Open Bio, 11(1), 300-311. https://doi.org/10.1002/2211-5463.13027
Zhang H, et al. 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. FEBS Open Bio. 2021;11(1):300-311. PubMed PMID: 33155431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Zhang,Hui, AU - Zhang,Xue-Mei, AU - Zong,Dan-Dan, AU - Ji,Xiao-Ying, AU - Jiang,Hua, AU - Zhang,Feng-Zheng, AU - He,Sheng-Dong, Y1 - 2020/12/16/ PY - 2020/09/28/received PY - 2020/10/21/revised PY - 2020/11/04/accepted PY - 2020/11/7/pubmed PY - 2021/12/15/medline PY - 2020/11/6/entrez KW - CGRP KW - COX2 KW - PGE2 KW - SIRT1 KW - miR-34a-5p KW - migraine SP - 300 EP - 311 JF - FEBS open bio JO - FEBS Open Bio VL - 11 IS - 1 N2 - 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. SN - 2211-5463 UR - https://www.unboundmedicine.com/medline/citation/33155431/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_ L2 - https://doi.org/10.1002/2211-5463.13027 DB - PRIME DP - Unbound Medicine ER -