Ciliary neurotrophic factor-treated astrocyte-conditioned medium increases the intracellular free calcium concentration in rat cortical neurons

Sun, Meiqun; Liu, Hongli; Min, Shengping; Wang, Hongtao; Wang, Xiaojing

doi:10.3892/br.2016.602

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…Six hours later, the cells were washed and cultured in DMEM at 37 °C, 5% CO 2 so that the background composition of CM is similar to SS with the only variable being the exosomes that astrocyte have secreted into CM. CM collected from serum-starved astrocytes was prepared by following the established protocol 8 , 53 , 54 .…”

Section: Methodsmentioning

confidence: 99%

TRPA1–FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

et al. 2017

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Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein–protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2, hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.

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Section: Methodsmentioning

confidence: 99%

TRPA1–FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

et al. 2017

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“…Pico-to nanomolar concentrations of CNTF, well within its physiological range (Sun et al, 2016), elevated the cholinergic marker genes CHAT (PDay3 = 0.005, PDay4 = 4.1E-05) and SLC18A3 (aka vAChT, PDay2 = 0.002, PDay4 = 0.001). In the female-originated LA-N-2 cells, CHAT elevation was visible at low concentrations and significant at medium concentrations ( Figure 4C).…”

Section: Neurokine-induced Cholinergic Differentiation Distinctly Altmentioning

confidence: 89%

Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Lobentanzer

Hanin

Klein

et al. 2019

Preprint

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135 words): RNA-sequencing analyses are often limited to identifying lowest p-value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA-sequencing of human male-and female-originated cell lines, and connectomics of transcription factor-and microRNA-interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. While these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method explicates the differences between afflicted men and women, and identifies diseaseaffected pathways of cholinergic transmission and gp130-family neurokine controllers of immune function, interlinked by microRNAs. This approach may open new perspectives for seeking biomarkers and therapeutic targets, also in other transmitter systems and diseases.Manuscript (Erta et al., 2012): the gp130 co-receptor (also known as IL6ST, IL-6 signal transducer), and the LIF-receptor. Gp130-family neurokines unite properties of neurotrophic (e.g. on dopaminergic neurons) and immunogenic nature, both prominent facets in the molecular etiology of SCZ and BD (Harrison, 2015) and in cholinergic signaling (Stanke et al., 2006). Neurokines can activate JAK1/2, TYK2 and STAT1/3/5A/5B (Rawlings, 2004), affecting neurotransmission as well as immunity. However, to the best of our knowledge, their roles in SCZ/BD were not yet studied.SCZ/BD hallmarks also involve circadian perturbations. The cholinergic-catecholaminergic imbalance in BD (Van Enkhuizen et al., 2015) follows variable transcriptionally-regulated rhythms (e.g. CLOCK, ARNTL, RORA), and affected individuals exhibit decreased REM latency (the duration from onset of sleep to the first rapid eye movement phase) and increased vulnerability for disease that can be modulated by muscarinic agonists/antagonists (Ising et al., 2005). Correspondingly, the muscarinic M1/M3 receptor genes are essential for REM sleep (Niwa et al., 2018), and sleep deprivation exerts short-term antidepressant effects (Wu and Bunney, 1990), reduced cortical ACh levels (Boonstra et al., 2007), and vast transcriptional changes in basal forebrain cholinergic neurons (Nikonova et al., 2017).The quantitative measurement of disease-relevance of individual perturbed genes is a common methodological problem in transcriptomic analyses. To reduce complexity, transcripts are often filtered by their p-values, leading to bias towards few highly expressed and differentially regulated genes. This does not agree with a polygenic model where each component contributes a small effect. To alleviate this bias while still attempting the necessary complexity reduction, we developed an integrative approach of multiple perspectives. Jerusalem and Andreas Meisel, Berlin and to Dr. Ester Bennett, Jerusalem ...

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“…Notably, the male-originated LA-N-5 cells responded more strongly to the neurokine stimulus, showing more DE miRNAs with a trend toward higher count-change values (mean of absolute countchange across all DE time points, 20,907 versus 3,066, p = 0.08). Pico-to nanomolar concentrations of CNTF, well within its physiological range (Sun et al, 2016), elevated the cholinergic marker genes CHAT (p value/day 3 of experiment [p Day3 ] = 0.005, p Day4 = 4.1EÀ05) and SLC18A3 (also known as vAChT, p Day2 = 0.002, p Day4 = 0.001). In female-originating LA-N-2 cells, CHAT elevation was visible at low concentrations and significant at medium concentrations ( Figure 4C).…”

Section: Short Rna Profiling Neurokine-induced Cholinergic Differentimentioning

confidence: 98%

Integrative Transcriptomics Reveals Sexually Dimorphic Control of the Cholinergic/Neurokine Interface in Schizophrenia and Bipolar Disorder

et al. 2019

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Graphical Abstract Highlights d Single-cell transcriptomes reveal a unique profile of cortical cholinergic neurons d Female-and male-derived cells show distinct neurokineinduced miRNA responses d Differentially enriched microRNA families constitute a selforganizing network d Integrative analysis identifies mir-10/mir-199 regulators of cholinergic function SUMMARYRNA sequencing analyses are often limited to identifying lowest p value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large-scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA sequencing of human male-and female-originating cell lines, and connectomics of transcription factor and microRNA interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. Although these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method reveals the differences between afflicted men and women and identifies disease-affected pathways of cholinergic transmission and gp130family neurokine controllers of immune function interlinked by microRNAs. This approach may open additional perspectives for seeking biomarkers and therapeutic targets in other transmitter systems and diseases.

show abstract

Ciliary neurotrophic factor-treated astrocyte-conditioned medium increases the intracellular free calcium concentration in rat cortical neurons

Cited by 3 publications

References 24 publications

TRPA1–FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

TRPA1–FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Integrative Transcriptomics Reveals Sexually Dimorphic Control of the Cholinergic/Neurokine Interface in Schizophrenia and Bipolar Disorder

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