scholarly journals Modulation of miR-146a/complement factor H-mediated inflammatory responses in a rat model of temporal lobe epilepsy

2016 ◽  
Vol 36 (6) ◽  
Author(s):  
Fang He ◽  
Bei Liu ◽  
Qiang Meng ◽  
Yang Sun ◽  
Weiwen Wang ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Chronic Phase ◽  
Factor H ◽  
Complement Factor H ◽  
Luciferase Reporter ◽  
Complement Factor ◽  
Small Regulatory Rna

Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy (TLE). miRNAs represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune system homoeostasis and function. We investigated the expression and cellular distribution of miRNA-146a (miR-146a) in a rat model of TLE. Prominent up-regulation of miR-146a activation was evident in 1 week after status epilepticus (SE) and persisted in the chronic phase. The predicted miR-146a's target complement factor H (CFH) mRNA and protein expression was also down-regulated in TLE rat model. Furthermore, transfection of miR-146a mimics in neuronal and glial cells down-regulated CFH mRNA and protein levels respectively. Luciferase reporter assays demonstrated that miR-146a down-regulated CFH mRNA expression via 3′-UTR pairing. Down-regulating miR-146a by intracerebroventricular injection of antagomir-146a enhanced the hippocampal expression of CFH in TLE model and decreased seizure susceptibility. These findings suggest that immunopathological deficits associated with TLE can in part be explained by a generalized miR-146a-mediated down-regulation of CFH that may contribute to epileptogenesis in a rat model of TLE.

scholarly journals Upregulation of Complement Factor H by SOCS-1/3–STAT4 in Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 471 ◽  
Author(s):  
Yeon-Hee Yoon ◽  
Hyeon-Ji Hwang ◽  
Hye-Jin Sung ◽  
Sun-Hee Heo ◽  
Dong-Sun Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Expression Patterns ◽  
Factor H ◽  
Complement Factor H ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Complement Factor ◽  
Low Level

Complement factor H (CFH) is a fluid phase regulator of complement proteins and functions to prevent complement attack and immune surveillance. CFH is known to inactivate therapeutic antibody-dependent complement-mediated cellular cytotoxicity. We found that CFH was highly expressed in human lung cancer cells and tissues. To investigate mechanisms of CFH upregulation, we searched for a CFH transcription factor and its regulatory factors. First, signal transducer and activator of transcription 4 (STAT4) expression patterns coincided with CFH expression patterns in lung cancer tissues. Knockdown of STAT4 led to decreased CFH secretion from lung cancer cells. STAT4 bound directly to the CFH promoter, as demonstrated by luciferase reporter assay, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP) assay, suggesting that STAT4 is a transcription factor for CFH. In addition, a low level of suppressors of cytokine signaling (SOCS)-1/3, a Janus kinase (JAK) inhibitor, was observed in lung cancer cells and its transfection decreased CFH protein levels and promoter activity. Unexpectedly, the low level of SOCS-1/3 was not due to epigenetic silencing. Instead, differential methylation was found on the regulatory region of STAT4 between normal and lung cancer cells. In conclusion, our results demonstrated that CFH is upregulated by constitutive activation of STAT4, which is accounted for by SOCS silencing in lung cancer cells.

Intravitreal human complement factor H in a rat model of laser-induced choroidal neovascularisation

2012 ◽  
Vol 97 (3) ◽  
pp. 367-370 ◽  
Author(s):  
Sang Jin Kim ◽  
Jaeryung Kim ◽  
Jinyoung Lee ◽  
Sung Yoon Cho ◽  
Hee Jung Kang ◽  
...  
Keyword(s):  
Rat Model ◽  
Choroidal Neovascularisation ◽  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
Human Complement

scholarly journals Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy

2020 ◽  
Vol 22 (5) ◽  
pp. 1197-1207 ◽  
Author(s):  
Maria Elisa Serrano ◽  
Mohamed Ali Bahri ◽  
Guillaume Becker ◽  
Alain Seret ◽  
Charlotte Germonpré ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Kainic Acid ◽  
Temporal Lobe ◽  
Rat Model ◽  
Chronic Phase ◽  
Male Rats ◽  
Saline Control ◽  
Control Group ◽  
Significant Group

Abstract Purpose The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. Procedures Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [18F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. Results Control rats presented a significant increase in [18F]UCB-H binding at the last two scans, compared with the first ones (p < 0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p < 0.028). Furthermore, the quantification of the SV2A expression in vivo with the [18F]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both. Conclusions Even if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [18F]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease.

scholarly journals Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Hui Huang ◽  
Guiyun Cui ◽  
Hai Tang ◽  
Lingwen Kong ◽  
Xiaopeng Wang ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Rat Model ◽  
Cell Apoptosis ◽  
Neuronal Damage ◽  
Luciferase Reporter ◽  
Caspase 9 ◽  
Notch 1 ◽  
Expression Levels ◽  
Gene Assay

AbstractThis study aimed to evaluate the specific regulatory roles of microRNA-146a (miRNA-146a) in temporal lobe epilepsy (TLE) and explore the related regulatory mechanisms. A rat model of TLE was established by intraperitoneal injection of lithium chloride-pilocarpine. These model rats were injected intracerebroventricularly with an miRNA-146a inhibitor and Notch-1 siRNA. Then, neuronal damage and cell apoptosis in the cornu ammonis (CA) 1 and 3 regions of the hippocampus were assessed. SOD and MDA levels in the hippocampus were detected by chromatometry, and IL-1β, IL-6, and IL-18 levels were detected by ELISA. Then, we evaluated the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus. The interaction between Notch-1 and miRNA-146a was assessed by a dual luciferase reporter gene assay. A rat model of TLE was successfully established, which exhibited significantly increased miRNA-146a expression in the hippocampus. Silencing of miRNA-146a significantly alleviated the neuronal damage and cell apoptosis in the CA1 and CA3 regions of the hippocampus in TLE rats and decreased MDA, IL-1β, IL-6, and IL-18 levels and increased SOD levels in the hippocampus of TLE rats. In addition, silencing of miRNA-146a significantly decreased the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus of TLE rats. Notch-1 was identified as a target of miRNA-146a and silencing of Notch-1 aggravated the neuronal damage in the CA1 and CA3 regions. Silencing of miRNA-146a alleviated the neuronal damage in the hippocampus of TLE rats by down-regulating Notch-1.

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