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.
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.
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miR-34a-5p上调大鼠三叉神经节神经元中IL-1β/COX2/PGE2炎症通路并通过抑制SIRT1诱导CGRP释放
DOI：
10.1002/2211-5463.13027
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发表时间：
2021-01
期刊：
影响因子：
2.6
通讯作者：
He SD
中科院分区：
文献类型：
--
作者：
Zhang H;Zhang XM;Zong DD;Ji XY;Jiang H;Zhang FZ;He SD
miR-34 a-5 p上调IL-1β/COX 2/PGE 2炎症通路，并通过抑制三叉神经节神经元中SIRT 1的表达诱导细胞凋亡和降钙素基因相关肽的释放。这表明miR-34 a-5 p可能有潜力发展成为治疗偏头痛的治疗靶点。 偏头痛是一种使人衰弱的神经系统疾病，全球男性患病率为10.68%，女性为18.79%。阐明偏头痛的分子机制对于改善患者的生活质量具有重要意义。神经肽降钙素基因相关肽（CGRP）从三叉神经末梢的释放参与偏头痛的发病机制。最近的研究表明，miR-34 a-5 p表达的上调与急性偏头痛发作有关。在这里，我们研究了miR-34 a-5 p表达的改变是否会诱导血管活性肽CGRP的释放。我们分离了原代大鼠三叉神经节神经元，并进行了功能获得和功能丧失试验，以改变miR-34 a-5 p的表达水平。下调miR-34 a-5 p可抑制三叉神经节中白细胞介素-1 β（IL-1β）/环氧合酶2（COX 2）/前列腺素E2（PGE 2）的表达，减少IL-1β、PGE 2和CGRP的释放，上调沉默信息调节因子1（SIRT 1）的表达;而过表达miR-34 a-5 p可增强IL-1β/COX 2/PGE 2的表达，增加IL-1β、PGE 2和CGRP的释放，降低三叉神经节SIRT 1的表达。此外，miR-34 a-5 p的过表达诱导原代大鼠三叉神经元的凋亡。总之，这些发现表明miR-34 a-5 p通过抑制三叉神经节神经元中SIRT 1的表达上调IL-1β/COX 2/PGE 2炎症通路，诱导细胞凋亡并增强CGRP的释放;因此，miR-34 a-5 p可能具有作为治疗偏头痛的治疗靶点的潜力。
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.
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影响因子：
--
作者：
Russo, Andrew F.
通讯作者：
Russo, Andrew F.
DOI：
10.1146/annurev-pharmtox-010814-124701
发表时间：
2015
影响因子：
12.5
作者：
Russo AF
通讯作者：
Russo AF
影响因子：
7.4
作者：
Noseda R;Burstein R
通讯作者：
Burstein R
影响因子：
3.7
作者：
Yang H;Zhang W;Pan H;Feldser HG;Lainez E;Miller C;Leung S;Zhong Z;Zhao H;Sweitzer S;Considine T;Riera T;Suri V;White B;Ellis JL;Vlasuk GP;Loh C
通讯作者：
Loh C
miR-34a-5p 通过靶向心肌细胞中的 ZEB1 加剧缺氧诱导的细胞凋亡。
影响因子：
3.7
作者：
Shi, Kaiyao;Sun, Huan;Yu, Bo
通讯作者：
Yu, Bo