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Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation
Experimental Brain Research ( IF 2 ) Pub Date : 2021-09-09 , DOI: 10.1007/s00221-021-06194-6
Weidong Liu 1 , Benfang Pu 2 , Mindi Liu 2 , Xuejun Zhang 2 , Ran Zeng 2
Affiliation  

Our objective of this study is to determine the molecular mechanism of MAPKs (mitogen activated protein kinase systems) on TRPV4 (transient receptor potential vanilloid 4)-mediated trigeminal neuralgia (TN). Partial chronic constriction injury of the infraorbital nerve (CCI-ION) ligation model was used in this research. When treated with antagonists of p38, JNK or ERK, the mechanical hyperalgesia threshold, nerve fiber disorder, myelinoclasis, and Schwann cells proliferation could be reversed. RT-PCR (real-time quantitative polymerase chain reaction), Western blot and IHC (immunohistochemistry) showed that TRPV4 mRNA and protein levels, TRPV4-positive cells and small positive neurons decreased remarkably in TN group treated with antagonists of p38, JNK or ERK. ELISA (enzyme-linked immunosorbent assay) was performed to discover inhibition of MAPK pathway can down-regulate the expression of HATs (histone acetyltransferases), and up-regulate the expression of HDACs (histone deacetylases) in TN, thus inhibiting histone acetylation. Finally, Western blot was performed to identify the phosphorylation status of p38, JNK and ERK, finding decreased phosphorylation forms in antagonists treated TN groups compared with TN groups. Based on the above investigation method, on a whole, our study showed that down-regulation of MAPK pathway could alleviate TRPV4-mediated trigeminal neuralgia, via inhibiting the activation of histone acetylation.



中文翻译:

MAPK通路的下调通过抑制组蛋白乙酰化的激活来缓解TRPV4介导的三叉神经痛

我们本研究的目的是确定 MAPK(丝裂原活化蛋白激酶系统)对 TRPV4(瞬时受体电位香草酸 4)介导的三叉神经痛 (TN) 的分子机制。本研究采用眶下神经部分慢性缩窄性损伤(CCI-ION)结扎模型。当用 p38、JNK 或 ERK 的拮抗剂治疗时,可以逆转机械痛觉过敏阈值、神经纤维紊乱、髓鞘破裂和雪旺氏细胞增殖。RT-PCR(实时定量聚合酶链反应)、Western印迹和IHC(免疫组织化学)显示,在用p38、JNK或ERK拮抗剂处理的TN组中,TRPV4 mRNA和蛋白水平、TRPV4阳性细胞和小阳性神经元显着降低。 . ELISA(酶联免疫吸附试验)发现抑制 MAPK 通路可下调 HATs(组蛋白乙酰转移酶)的表达,上调 TN 中 HDACs(组蛋白脱乙酰酶)的表达,从而抑制组蛋白乙酰化。最后,进行蛋白质印迹以鉴定 p38、JNK 和 ERK 的磷酸化状态,发现与 TN 组相比,拮抗剂处理的 TN 组中磷酸化形式降低。基于上述研究方法,我们的研究总体上表明,下调MAPK通路可以通过抑制组蛋白乙酰化的激活来缓解TRPV4介导的三叉神经痛。从而抑制组蛋白乙酰化。最后,进行蛋白质印迹以鉴定 p38、JNK 和 ERK 的磷酸化状态,发现与 TN 组相比,拮抗剂处理的 TN 组中磷酸化形式降低。基于上述研究方法,我们的研究总体上表明,下调MAPK通路可以通过抑制组蛋白乙酰化的激活来缓解TRPV4介导的三叉神经痛。从而抑制组蛋白乙酰化。最后,进行蛋白质印迹以鉴定 p38、JNK 和 ERK 的磷酸化状态,发现与 TN 组相比,拮抗剂处理的 TN 组中磷酸化形式降低。基于上述研究方法,我们的研究总体上表明,下调MAPK通路可以通过抑制组蛋白乙酰化的激活来缓解TRPV4介导的三叉神经痛。

更新日期:2021-09-09
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