microRNA-200b modulates microglia-mediated neuroinflammation via the cJun/MAPK pathway
TL;DR: Results indicate that miRNA‐200b modulates microglial inflammatory process including cytokine secretion, NO production, migration and neuronal survival.
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Abstract: Chronic activation of microglia, the macrophages of the CNS, has been shown to enhance neuronal damage because of excessive release of proinflammatory cytokines and neurotoxic molecules in a number of neurodegenerative diseases. Recent reports showed altered microRNA (miRNA) expression in immune-mediated pathologies, thus suggesting that miRNAs modulate expression of genes involving immune responses. This study demonstrates that miRNA-200b is expressed in microglia and modulates inflammatory response of microglia by regulating mitogen-activated protein kinase pathway. miRNA-200b expression was found to be down-regulated in activated microglia in vivo (traumatic brain injury rat model) and in vitro. A luciferase assay and loss- and gain-of-function studies revealed c-Jun, the transcription factor of cJun-N terminal kinase (JNK) mitogen-activated protein kinase pathway to be the target of miR-200b. Knockdown of miR-200b in microglia increased JNK activity along with an increase in pro-inflammatory cytokines, inducible nitric oxide synthase expression and nitric oxide (NO) production. Conversely, over-expression of miRNA-200b in microglia resulted in a decrease in JNK activity, inducible nitric oxide synthase expression, NO production and migratory potential of activated microglia. Furthermore, miR-200b inhibition resulted in increased neuronal apoptosis after treatment of neuronal cells with conditioned medium obtained from microglial culture. Taken together, these results indicate that miRNA-200b modulates microglial inflammatory process including cytokine secretion, NO production, migration and neuronal survival.
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References
Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death.
Yuichi Hashimoto,Osahiko Tsuji,Takako Niikura,Yohichi Yamagishi,Miho Ishizaka,Masaoki Kawasumi,Tomohiro Chiba,Kohsuke Kanekura,Marina Yamada,Emi Tsukamoto,Keisuke Kouyama,Kenzo Terashita,Sadakazu Aiso,Anning Lin,Ikuo Nishimoto +14 more
TL;DR: It is demonstrated that JNK is involved in APP‐mediated neuronal cell death as a downstream signal transducer of Go, and the pharmacological profile of caJNK‐mediated cell death closely coincided with that of APP‐ mediated cell death.
100
MicroRNA Expression Profiling Reveals MiRNA Families Regulating Specific Biological Pathways in Mouse Frontal Cortex and Hippocampus
Juuso Juhila,Tessa Sipilä,Tessa Sipilä,Katherine Icay,Daniel Nicorici,Pekka Ellonen,Aleksi Kallio,Eija Korpelainen,Dario Greco,Iiris Hovatta +9 more
TL;DR: A miRNA-Seq approach with a bioinformatic analysis workflow that is suitable for studying miRNA expression patterns from specific brain nuclei is developed and can be applied for the identification of brain region-specific and phenotype-specific mi RNA-mRNA-regulatory networks from the adult and developing rodent brain.
Radiation-induced c-Jun activation depends on MEK1-ERK1/2 signaling pathway in microglial cells.
TL;DR: This study reveals that the MEK-ERK1/2 signaling pathway, but not the JNK pathway, contributes to the c-Jun-dependent microglial inflammatory response following irradiation.
MicroRNA Expression Profiling Reveals MiRNA Families Regulating Specific Biological Pathways in Mouse Frontal Cortex and Hippocampus
Juuso Juhila,Tessa Sipilä,Tessa Sipilä,Katherine Icay,Daniel Nicorici,Pekka Ellonen,Aleksi Kallio,Eija Korpelainen,Dario Greco,Iiris Hovatta +9 more
- 01 Jan 2011
TL;DR: In this paper, the miRNA expression patterns by miRNA-Seq and micro-arrays in two brain regions, frontal cortex (FCx) and hippocampus (HP), were studied.
72
The TAT-JNK inhibitor peptide interferes with beta amyloid protein stability.
Alessio Colombo,Mariaelena Repici,M Pesaresi,Sara Santambrogio,Gianluigi Forloni,Tiziana Borsello,Tiziana Borsello +6 more
TL;DR: JNK’s role in APP phosphorylation in cortical neurons, using the JNK inhibitor D-JNKI1, was focused on, with a clear decrease in the secreted APP (APPs) in the media of treated neurons.