GeoHealth
·
2024
·Vol. 8
·期 4
·e2023GH000888
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IF 4.3
Xiaoning Wang,Xin Sui,Yangyang Sun,Ziqi Cui,Ning Ma,Shuai Wang,Jun Yang,Fengying Liu,Weijie Yang,Zhenyu Xiao,Tong Zhu,Yuan Luo,Yongan Wang
The Multi-Threat Medical Countermeasure (MTMC) technique is crucial for developing common biochemical signaling pathways, molecular mediators, and cellular processes. This study revealed that the Nod-like receptor 3 (NLRP3) inflammasome pathway may be a significant contributor to the cytotoxicity induced by various organophosphorus pesticides (OPPs). The study demonstrated that exposure to six different types of OPPs (paraoxon, dichlorvos, fenthion, dipterex, dibrom, and dimethoate) led to significant cytotoxicity in BV2 cells, which was accompanied by increased expression of NLRP3 inflammasome complexes (NLRP3, ASC, Caspase-1) and downstream inflammatory cytokines (IL-1β, IL-18), in which the order of cytotoxicity was dichlorvos > dipterex > dibrom > paraoxon > fenthion > dimethoate, based on the IC 50 values of 274, 410, 551, 585, 2,158, and 1,527,566 μM, respectively. The findings suggest that targeting the NLRP3 inflammasome pathway could be a potential approach for developing broad-spectrum antitoxic drugs to combat multi-OPPs-induced toxicity. Moreover, inhibition of NLRP3 efficiently protected the cells against cytotoxicity induced by these six OPPs, and the expression of NLRP3, ASC, Caspase-1, IL-1β, and IL-18 decreased accordingly. The order of NLRP3 affinity for OPPs was dimethoate > paraoxon > dichlorvos > dibrom > (fenthion and dipterex) based on K D values of 89.8, 325, 1,460, and 2,690 μM, respectively. Furthermore, the common molecular mechanism of NLRP3-OPPs was clarified by the presence of toxicity effector groups (benzene ring, nitrogen/oxygen-containing functional group); =O, -O-, or =S (active) groups; and combination residues (Gly271, Asp272). This finding provided valuable insights into exploring the common mechanisms of multiple threats and developing effective therapeutic strategies to prevent OPPs poisoning. Key Points The NLRP3 inflammasome potentially contributes to cytotoxicity induced by six types of OPPs Inhibition of the NLRP3 pathway effectively prevented cytotoxicity caused by six OPPs The study proposed targets for broad-spectrum antitoxic drugs to prevent OPPs-poisoning Plain Language Summary This study aimed to explore the role of Nod-like receptor 3 (NLRP3) inflammasome activation in organophosphorus pesticide (OPPs)-induced cytotoxicity. Six different OPPs, including dimethoate, paraoxon, dichlorvos, dibrom, fenthion, and dipterex, were introduced to BV2 cells and caused significant cytotoxicity along with increased expression of NLRP3 inflammasome complexes and downstream cytokines. Inversely, inhibition of NLRP3 protected against these OPPs. We believe that our study makes a significant contribution to the literature because it suggests that the NLRP3 inflammasome pathway may be a common mechanism of multi-OPPs-induced cytotoxicity. By introducing a therapeutic target for OPPs poisoning prevention, broad-spectrum antitoxic drugs may be designed to effectively protect against OPPs-induced cytotoxicity.
研究领域:
毒理学
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免疫学
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药理学
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DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
·
2024
·
IF 4.6
Weng Jiyu,Wang Ying,Tan Zekai,Yuan Yanghe,Huang Shiyuan,Li Zexi,Li Yiming,Zhang Lanyue,Du Zhiyun
Objectives Chronic neuroinflammation has become one of the important causes of common neurodegeneration disease. Therefore, the target of this study was to explore the protective action of glabridin on lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro and its mechanism. Methods The neuroinflammation model was established by LPS-induced BV2 cells. The cell viability with various concentrations of glabridin was determined by MTT assay, and the content of NO in each group was detected. A neuroinflammatory model was established in male C57BL/6J mice for a water maze test. Subsequently, NF-κB and SOD indices were measured by ELISA, GFAP and IBA-1 indices were measured by immunofluorescence, and Nissl staining was used to explore the Nissl bodies in the hippocampus of mice. Results In vitro experiments, our results expressed that glabridin could markedly increase the cell activity of LPS-induced BV2 cells and reduce the NO expression in cells. It indicated that glabridin had a remarkable impact on the neuroinflammation of LPS-induced BV2 cell protection. In vivo neuroinflammation experiments, mice treated with different doses of glabridin showed significantly improved ability of memory compared with the LPS group in the Morris water maze test. The levels of NF-κB, GFAP, and the number of positive cells in Nissl staining were decreased. High-dose glabridin significantly increased the SOD content in the brain tissue and decreased the IBA-1 levels. Conclusion Glabridin can significantly reduce or even reverse LPS-induced neuroinflammation, which may be related to the fact that glabridin can reduce the NO expression, NF-κB, IBA-1, GFAP, and other inflammatory mediators, upregulate the expression of SOD to relieve oxidative stress of brain and inhibit the activation of gliocyte in brain tissue.
研究领域:
神经科学
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药理学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2019
·
IF 2.431
Jingwen Li,Menglong Duan,Xinsheng Yao,Danmei Tian,Jinshan Tang
Phytochemical studies of the air-dried pericarp of Citrus grandis led to the isolation of four new compounds including three prenylated benzenepropanoic acids ( 2 , 3 and 5 ) and one alkamidic glycoside ( 6 ), together with ten known compounds ( 1 , 4 and 7 – 14 ). The structures of these compounds were determined by the NMR spectroscopy, optical rotation data and modified Mosher's method. Meanwhile, the anti-neuroinflammatory activities of all isolated compounds were evaluated by detecting the production of nitric oxide (NO) in LPS-stimulated BV2 cells. The results showed that compounds 1 , 2 , 5 and 13 exhibited strong inhibition effects on NO production in LPS-stimulated BV2 cells. Mechanistically, compounds 1 , 2 and 5 could suppress the expressions of iNOS. In addition, compounds 1 , 2 and 5 also showed obvious inhibition effects on COX-2 expression, another vital enzyme in the inflammation process, in LPS-treated BV2 cells. These findings shed light on the potent anti-neuroinflammatory effects of Citrus grandis .
研究领域:
药理学
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神经科学
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植物化学
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产品关联
DOI
PubMed
高影响因子
IMMUNOLOGICAL INVESTIGATIONS
·
2024
·
IF 2.9
Wei Zhang,Chengcheng Fan,Zhongxue Yi,Tao Du,Nana Wang,Weizhu Tian,Qian Pan,Xiande Ma,Zhe Wang
Background Cerebral ischemia/reperfusion injury (CIRI) is still a complicated disease with high fatality rates worldwide. Transmembrane Protein 79 (TMEM79) regulates inflammation and oxidative stress in some other diseases.Methods CIRI mouse model was established using C57BL/6J mice through middle cerebral artery occlusion-reperfusion (MCAO/R), and BV2 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to simulate CIRI. Brain tissue or BV2 cells were transfected or injected with lentivirus-carried TMEM79 overexpression vector. The impact of TMEM79 on CIRI-triggered oxidative stress was ascertained by dihydroethidium (DHE) staining and examination of oxidative stress indicators. Regulation of TMEM79 in neuronal apoptosis and inflammation was determined using TUNEL staining and ELISA.Results TMEM79 overexpression mitigated neurological deficit induced by MCAO/R and decreased the extent of cerebral infarct. TMEM79 prevented neuronal death in brain tissue of MCAO/R mouse model and suppressed inflammatory response by reducing inflammatory cytokines levels. Moreover, TMEM79 significantly attenuated inflammation and oxidative stress caused by OGD/R in BV2 cells. TMEM79 facilitated the activation of Nrf2 and inhibited NLRP3 and caspase-1 expressions. Rescue experiments indicated that the Nrf2/NLRP3 signaling pathway mediated the mitigative effect of TMEM79 on CIRI in vivo and in vitro.Conclusion Overall, TMEM79 was confirmed to attenuate CIRI via regulating the Nrf2/NLRP3 signaling pathway.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2024
·
IF 3.5
Shipeng Li,Ping Yang,Zhenghan Wu,Wenqiang Huang,Xiaofeng Zhu,Lianmei Zhong
Objective Research has shown that cerebral ischemia-reperfusion injury (CIRI) involves a series of physiological and pathological mechanisms, including inflammation, oxidative stress, and cell apoptosis. The cannabinoid receptor 2 agonist AM1241 has been found to have anti-inflammatory and anti-oxidative stress effects. However, it is unclear whether AM1241 has a protective effect against brain ischemia-reperfusion injury, and its underlying mechanisms are not yet known. Methods In this study, we investigated the anti-inflammatory, anti-oxidative stress, and anti-apoptotic effects of AM1241 and its mechanisms in BV2 cells stimulated with H 2 O 2 and in a C57BL/6 mouse model of CIRI in vitro and in vivo , respectively. Results In vitro , AM1241 significantly inhibited the release of pro-inflammatory cytokines TNF-α and IL-6, reactive oxygen species (ROS), and the increase in Toll-like receptor 4/myeloid differentiation protein 2 (MD2/TLR4) complex induced by H 2 O 2 . Under H 2 O 2 stimulation, MD2 overexpression resulted in increased levels of MD2/TLR4 complex, TNF-α, IL-6, NOX2, BAX, and Cleaved-Caspase3 (C-Caspase3), as well as the activation of the MAPK pathway and NF-κB, which were reversed by AM1241. In addition, molecular docking experiments showed that AM1241 directly interacted with MD2. Surface Plasmon Resonance (SPR) experiments further confirmed the binding of AM1241 to MD2. In vivo , AM1241 significantly attenuated neurofunctional impairment, brain edema, increased infarct volume, oxidative stress levels, and neuronal apoptosis in CIRI mice overexpressing MD2. Conclusion Our study demonstrates for the first time that AM1241 alleviates mouse CIRI by inhibiting the MD2/TLR4 complex, exerting anti-inflammatory, anti-oxidative stress and anti-apoptotic effects.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Zhi-shen Xie,Jian-ping Zhao,Li-min Wu,Shuang Chu,Zheng-hao Cui,Yi-ran Sun,Hui Wang,Hui-fen Ma,Dong-rui Ma,Pan Wang,Xiao-wei Zhang,Zhen-qiang Zhang
Background Autophagic flux is coordinated by a network of master regulatory genes, which centered on transcription factor EB (TFEB). The disorders of autophagic flux are closely associated with Alzheimer's disease (AD), and thus restoring autophagic flux to degrade pathogenic proteins has become a hot therapeutic strategy. Hederagenin (HD), a triterpene compound, isolated from a variety food such as Matoa (Pometia pinnata) Fruit, Medicago sativa, Medicago polymorpha L. Previous studies have shown that HD has the neuroprotective effect. However, the effect of HD on AD and underlying mechanisms are unclear. Purpose To determine the effect of HD on AD and whether it promotes autophagy to reduce AD symptoms. Study Design BV2 cells , C. elegans and APP/PS1 transgenic mice were used to explore the alleviative effect of HD on AD and the molecular mechanism in vivo and in vitro . Methods The APP/PS1 transgenic mice at 10 months were randomized into 5 groups ( n = 10 in each group) and orally administrated with either vehicle (0.5% CMC Na), WY14643 (10 mg/kg/d), low-dose of HD (25 mg/kg/d), high-dose of HD (50 mg/kg/d) or MK-886 (10 mg/kg/d) + HD (50 mg/kg/d) for consecutive 2 months. The behavioral experiments including morris water maze test, object recognition test and Y maze test were performed. The effects of HD on Aβ deposition and alleviates Aβ pathology in transgenic C. elegans were operated using paralysis assay and fluorescence staining assay. The roles of HD in promoting PPARα/TFEB-dependent autophagy were investigated using the BV2 cells via western blot analysis, real-time quantitative PCR (RT-qPCR), molecular docking, molecular dynamic (MD) simulation, electron microscope assay and immunofluorescence. Results In this study, we found that HD upregulated mRNA and protein level of TFEB and increased the distribution of TFEB in the nucleus, and the expressions of its target genes. HD also promoted the expressions of LC3BII/LC3BI, LAMP2, etc. , and promoted autophagy and the degradation of Aβ. HD reduced Aβ deposition in the head area of C. elegans and Aβ-induced paralysis. HD improved cognitive impairment and pathological changes in APP/PS1 mice by promoting autophagy and activating TFEB. And our results also showed that HD could strongly target PPARα. More importantly, these effects were reversed by treatment of MK-886, a selective PPARα antagonist. Conclusion Our present findings demonstrated that HD attenuated the pathology of AD through inducing autophagy and the underlying mechanism associated with PPARα/TFEB pathway.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Ziliang He,Yeye Hu,Ying Zhang,Jing Xie,Zhiqiang Niu,Guigui Yang,Ji Zhang,Zixuan Zhao,Shuai Wei,Haifeng Wu,Weicheng Hu
Background Parkinson's disease (PD), a neurodegenerative disorder, is characterized by motor symptoms due to the progressive loss of dopaminergic neurons in the substantia nigra (SN) and striatum (STR), alongside neuroinflammation. Asiaticoside (AS), a primary active component with anti-inflammatory and neuroprotective properties, is derived from Centella asiatica. However, the precise mechanisms through which AS influences PD associated with inflammation are not yet fully understood. Purpose This study aimed to explore the protective mechanism of AS in PD. Methods Targets associated with AS and PD were identified from the Swiss Target Prediction, Similarity Ensemble Approach, PharmMapper, and GeneCards database. A protein-protein interaction (PPI) network was constructed to identify potential therapeutic targets. Concurrently, GO and KEGG analyses were performed to predict potential signaling pathways. To validate these mechanisms, the effects of AS on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice were investigated. Furthermore, neuroinflammation and the activation of the NLRP3 inflammasome were assessed to confirm the anti-inflammatory properties of AS. In vitro experiments in BV2 cells were then performed to investigate the mechanisms of AS in PD. Moreover, CETSA, molecular docking, and molecular dynamics simulations (MDs) were performed for further validation. Results Network pharmacology analysis identified 17 potential targets affected by AS in PD. GO and KEGG analyses suggested the biological roles of these targets, demonstrating that AS interacts with 149 pathways in PD. Notably, the NOD-like receptor signaling pathway was identified as a key pathway mediating AS's effect on PD. In vivo studies demonstrated that AS alleviated motor dysfunction and reduced the loss of dopaminergic neurons in MPTP-induced PD mice. In vitro experiments demonstrated that AS substantially decreased IL-1β release in BV2 cells, attributing this to the modulation of the NLRP3 signaling pathway. CETSA and molecular docking studies indicated that AS forms a stable complex with NLRP3. MDs suggested that ARG578 played an important role in the formation of the complex. Conclusion In this study, we first predicted that the potential target and pathway of AS's effect on PD could be NLRP3 protein and NOD-like receptor signaling pathway by network pharmacology analysis. Further, we demonstrated that AS could alleviate symptoms of PD induced by MPTP through its interaction with the NLRP3 protein for the first time by in vivo and in vitro experiments. By binding to NLRP3, AS effectively inhibits the assembly and activation of the inflammasome. These findings suggest that AS is a promising inhibitor for PD driven by NLRP3 overactivation.
研究领域:
神经科学
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药理学
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炎症
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Qian Yu,Xian Qiu,Jing Zhong,Chao Cao,Yuechan Liao,Zhiwei Zeng,Dawei Zhang,Chunyan Yan
Acorus tatarinowii , a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF- α , IL-1 β , PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50–3 was obtained from AT50. Structural analysis indicated ATP50–3 consisted of α -L-Ara f -(1→, →2)- α -L-Ara f -(1→, →3)- α -L-Ara f -(1→, →5)- α -L-Ara f -(1→, α -D-Xyl p -(1→, →3,4)- β -D-Xyl p -(1→, →3)- α -D-Gal p -(1→, →3,6)- α -D-Gal p -(1→, →6)-4-OAc- α -D-Gal p -(1→, →3,4,6)- α -D-Gal p -(1→, →4)- α -D-Glc p -(1→, →2,3,6)- β -D-Glc p -(1→, →4,6)- α -D-Man p -(1→, →3,4)- α -L-Rha p -(1→, →4)- α -D-Gal p A-(1→, and →4)- α -D-Glc p A-(1 → residues and terminated with Xyl and Ara. Additionally, ATP50–3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50–3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.
研究领域:
药理学
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神经科学
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传统中药
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEUROTOXICITY RESEARCH
·
2021
·Vol. 39
·期 6
·1800-1811
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IF 3.911
Zhou Wei,Hu Mengmeng,Hu Jingrong,Du Zhiyun,Su Qing,Xiang Zhangmin
Microglia-mediated neuroinflammation in response to injurious self and non-self-stimuli exerts detrimental effects on neurons, which may lead to cognitive impairment. Luteolin, a typical kind of natural flavonoid in honeysuckle, chrysanthemum, and Herba Schizonepetae , is widely recognized to be anti-inflammatory and antioxidant against peripheral inflammation. However, its protective effect against inflammation-induced cognitive impairment is currently unknown. In this paper, we investigated the relief potential of luteolin against lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated BV2 microglia cells. In this study, luteolin ameliorated LPS-induced cognitive impairments, indicated by behavioral performance of neuroinflammatory model mice in Morris water maze tests. Protein analyses and histological examination also revealed protective effect of luteolin against neuronal damage, through inhibiting overproduction of inflammatory cytokines in both hippocampus and cortex of mice. We also observed luteolin in vitro significantly suppressed the levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 β (IL-1β), and inflammatory mediators like nitric oxide. Taken together, these results demonstrated luteolin was effective in alleviating cognitive impairment and limited neuronal damage via inhibiting the release of inflammatory mediators, suggesting luteolin is potential for further therapeutic research of neuroinflammation-related neurodegenerative diseases.
研究领域:
神经科学
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药理学
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免疫学
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
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IF 4.4
Yu Wenjing,Luo Rongsiqing,He Chunxiang,Li Ze,Yang Miao,Zhou Jinyong,He Jiawei,Chen Qi,Song Zhenyan,Cheng Shaowu
Background: The escalating global burden of diabetes and its associated cognitive impairment underscores the urgency for effective interventions. Bergenin shows promise in regulating glucose metabolism, mitigating inflammation, and improving cognitive function. Zebrafish models offer a unique platform for assessing drug efficacy and exploring pharmacological mechanisms, complemented by subsequent investigations in cell and rat models.Methods: The experimental subjects included zebrafish larvae (CZ98:Tg (mpeg1:EGFP)ihb20Tg/+), adult zebrafish (immersed in 2% glucose), BV2 cell line (50 mM glucose + 10 μm Aβ1-42), and a streptozotocin (STZ) bilateral intracerebroventricular injection rat model. Bergenin’s effects on the toxicity, behavior, and cognitive function of zebrafish larvae and adults were evaluated. The Morris water maze assessed cognitive function in rats. Neuronal histopathological changes were evaluated using HE and Nissl staining. qPCR and Western blot detected the expression of glycolysis enzymes, inflammatory factors, and Bergenin’s regulation of PPAR/NF-κB pathway in these three models.Results: 1) In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased ins expression and increased expression of irs1, irs2a, and irs2b, suggesting a reduction in insulin resistance. It also altered the expression of pparg and rela. 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1β, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus.Conclusion: Bergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.
研究领域:
药理学
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神经科学
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糖尿病
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炎症
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代谢
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行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2024
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IF 4.6
Yu Shan,Yang Jinghui,Zhang Rui,Guo Qian,Wang Lu
Systemic inflammatory stimulus is a risk factor for the incidence of ischemic stroke and contributes to poorer clinical outcomes. Solute carrier 15A3 (SLC15A3) is a peptide/histidine transporter that is implicated in regulating inflammatory responses. However, whether SLC15A3 affects the progression of ischemic stroke associated with systemic inflammation is unclear. The transient middle cerebral artery occlusion (tMCAO) mice with LPS administration (LPS/tMCAO) were prepared as an in vivo model, and LPS-induced BV2 cells under oxygen–glucose deprivation (OGD) exposure were utilized as an in vitro model. We found that SLC15A3 was highly expressed in the ischemic penumbra of LPS/tMCAO mice, and its inhibition reduced infarct area, attenuated neurological deficit, recovered motor function, and mitigated apoptotic neurons. Knockdown of SLC15A3 suppressed the proinflammatory M1-type markers and promoted the levels of M2-associated genes. The in vitro results confirmed that SLC15A3 overexpression promoted microglia polarizing towards M1 subtypes, while SLC15A3 inhibition exerted an opposite effect. In addition, we demonstrated that the p65 signaling pathway and HIF1α were activated by LPS/OGD. Luciferase reporter assay showed that inhibiting p65 using its specific inhibitor BAY 11–7082 or silencing HIF1α using siRNAs reduced the transcriptional activity of SLC15A3 in LPS/OGD-induced BV2 cells. Results in NIH 3T3 cells also confirmed that p65 and HIF1α directly bound to the SLC15A3 promoter to activate SLC15A3 transcription. In conclusion, this work shows that SLC15A3 , transcriptionally activated by p65 and HIF1α, contributes to poor outcomes in ischemic stroke associated with systemic inflammation by promoting microglial cells polarizing towards M1 types.
研究领域:
神经科学
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免疫学
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分子生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR NEUROSCIENCE
·
2019
·Vol. 68
·期 2
·181-190
·
IF 2.577
Yan Penghui,Wu Xuejian,Liu Xiaokang,Cai Yingchun,Shao Chenglong,Zhu Guangduo
Microglial activation and inflammatory response played an important role in the secondary injury of spinal cord injury (SCI). Several microRNAs were associated with this procedure, but the underlying molecular mechanism was poorly understood. Sprague-Dawley (SD) rats were divided into four groups: SCI group ( n = 7), agomiR-325-3p group ( n = 7), and their control groups. Expression of miR-325-3p and proteins in epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway was evaluated in microglia from SCI rats and primary microglia/BV2 cells activated by lipopolysaccharide (LPS). Concentrations of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in supernatants were measured by ELISA. Low expression of miR-325-3p and activation of EGFR/MAPK was observed in microglia of SCI and LPS-induced primary microglia. Overexpression of miR-325-3p in LPS-induced BV2 cells inhibited microglial activation and release of TNF-α and IL-1β. Luciferase reporter assay confirmed that miR-325-3p negatively regulated EGFR by targeting its 3′-untranslated regions. Additionally, agomiR-325-3p inhibited the activation of microglia and EGFR/MAPK, alleviating the inflammatory response. These results indicated that miR-325-3p attenuated secondary injury after SCI through inhibition of EGFR/MAPK signaling pathway, the microglial activation, and the release of inflammatory cytokines, suggesting that miR-325-3p may be employed as a therapeutic target for SCI.
研究领域:
神经科学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
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