Study on the Mechanism of Gm14461 Promoting Trigeminal Neuralgia by Recruiting CSTF2 to Upregulate CGRP and P2X3/7 Receptor Expression
10.3969/j.issn.1671-7414.2025.03.004
- VernacularTitle:Gm14461通过招募CSTF2上调CGRP和P2X3/7受体表达促进三叉神经痛的作用机制研究
- Author:
Kui WANG
1
;
Ke PAN
1
;
Li WU
1
Author Information
1. 恩施土家族苗族自治州中心医院神经外科,湖北 恩施 445000
- Publication Type:Journal Article
- Keywords:
trigeminal neuralgia;
Gm14461;
cleavage stimulation factor subunit 2;
calcitonin gene-related peptide;
P2X3/7 receptor
- From:
Journal of Modern Laboratory Medicine
2025;40(3):18-23,36
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of long non coding RNA(lncRNA)Gm14461 in promoting trigeminal neuralgia(TN)and its potential molecular mechanisms.Methods A TN mouse model was induced by surgery for chronic compression injury of the infraorbital nerve.Short hairpin RNA(shRNA)of Gm14461 was injected into TN mice,and the expression level of Gm14461 and mechanical pain threshold(MWT)in the trigeminal ganglia of the mice were measured.A TN cell model was established in vitro using tumor necrosis factor-α(TNF-α)to induce trigeminal ganglia,and the trigeminal ganglia were treated with sh-Gm14461 and cleavage stimulation factor subunit 2(CSTF2)overexpression vector(OE-CSTF2).RNA immunoprecipitation(RIP)analysis of CSTF2 binding to Gm14461,calcitonin gene-related peptide(CGRP),purine receptors P2X3 and P2X7 mRNA.Results Compared with the sham surgery group,the expression of Gm14461 in the trigeminal ganglia of TN group mice was significantly increased(t=35.450),and the MWT value of mice decreased in a time-dependent manner(t=8.427～28.190),with statistical significance(all P<0.05).The expression levels of inflammatory factors TNF-α,IL-1 β and IL-6,as well as pain related proteins CGRP,P2X3,and P2X7,were significantly increased in the trigeminal ganglia of TN mice,and the differences were statistically significant(t=31.750～50.240,all P<0.05).Knocking down Gm14461 significantly improved MWT(t=6.019～26.548),reduced inflammatory factors(t=43.959,26.416,25.431),and pain related protein levels(t=38.709,43.257,45.807)in TN mice,with statistically significant differences(all P<0.05).Compared with the control group,TNF-α induced upregulation of Gm14461 expression in the trigeminal ganglia(t=27.710),significantly increased levels of inflammatory factors and pain related protein expression(t=23.076～29.508),and the differences were statistically significant(all P<0.05).After knocking down Gm14461,the expression of Gm14461 was significantly reduced(t=3.641),and the levels of inflammatory factors and pain related proteins in the trigeminal ganglia induced by TNF-α were significantly reduced(t=20.560～25.136),with statistical significance(all P<0.05).Gm14461 upregulates CSTF2 protein levels by binding to CSTF2,and upregulates CSTF2 protein by binding to mRNA of CGRP,P2X3,and P2X7 and promoting their expression.Overexpression of CSTF2 can reverse the inhibitory effect of Gm14461 knockdown on TNF-α-induced inflammation and pain related protein expression in trigeminal ganglia(TGs)(t=18.870～24.399,all P<0.05).Conclusion Gm14461 upregulates the expression of CGRP,P2X3,and P2X7 by recruiting CSTF2,promotes inflammatory response,thereby reducing the mechanical pain threshold of TN mice and promoting pain.
