Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
作者全名："He, Ya; Zhang, Hongxia; Ma, Limin; Li, Jingang; Wang, Fei; Zhou, Hui; Zhang, Guangliang; Wen, Yuetao"
作者地址："[He, Ya] Chongqing Univ, Jiangjin Hosp, Dept Phys Examinat Ctr, Chongqing, Peoples R China; [Zhang, Hongxia] Chongqing Med Univ, Yongchuan Hosp, Dept Neurosurg, Chongqing, Peoples R China; [Ma, Limin] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing, Peoples R China; [Ma, Limin] Chongqing Univ, Gorges Hosp 1, Dept Neurol, Chongqing, Peoples R China; [Li, Jingang; Wang, Fei; Zhou, Hui; Zhang, Guangliang; Wen, Yuetao] Chongqing Univ, Jiangjin Hosp, Dept Neurosurg, Chongqing, Peoples R China"
通信作者："Wen, YT (通讯作者)，Chongqing Univ, Jiangjin Hosp, Dept Neurosurg, Chongqing, Peoples R China."
来源：JOURNAL OF NEUROINFLAMMATION
ESI学科分类：NEUROSCIENCE & BEHAVIOR
关键词：Temporal lobe epilepsy; Inflammation-related genes; Bioinformatics analysis; TIMP1; Biomarker
摘要："BackgroundEpilepsy is the second most prevalent neurological disease. Although there are many antiseizure drugs, approximately 30% of cases are refractory to treatment. Temporal lobe epilepsy (TLE) is the most common epilepsy subtype, and previous studies have reported that hippocampal inflammation is an important mechanism associated with the occurrence and development of TLE. However, the inflammatory biomarkers associated with TLE are not well defined.MethodsIn our study, we merged human hippocampus datasets (GSE48350 and GSE63808) through batch correction and generally verified the diagnostic roles of inflammation-related genes (IRGs) and subtype classification according to IRGs in epilepsy through differential expression, random forest, support vector machine, nomogram, subtype classification, enrichment, protein-protein interaction, immune cell infiltration, and immune function analyses. Finally, we detected the location and expression of inhibitor of metalloproteinase-1 (TIMP1) in epileptic patients and kainic acid-induced epileptic mice.ResultsAccording to the bioinformatics analysis, we identified TIMP1 as the most significant IRG associated with TLE, and we found that TIMP1 was mainly located in cortical neurons and scantly expressed in cortical gliocytes by immunofluorescence staining. We detected decreased expression of TIMP1 by quantitative real-time polymerase chain reaction and western blotting.ConclusionTIMP1, the most significant IRG associated with TLE, might be a novel and promising biomarker to study the mechanism of epilepsy and guide the discovery of new drugs for its treatment."
基金机构：Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX1005]
基金资助正文：This work was supported by the Natural Science Foundation of Chongqing which funded the author (Yuetao Wen; No. cstc2020jcyj-msxmX1005).