The effect of alcohol on the differential expression of cluster of differentiation 14 gene, associated pathways, and genetic network

Zhou, Diana; Zhao, Yinghong; Baker, Jessica A.; Gu, Qun; Hamre, Kristin; Yue, Junming; Jones, Byron C.; Cook, Melloni N.; Lu, Lu

doi:10.1371/journal.pone.0178689

Cited by 7 publications

(5 citation statements)

References 58 publications

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“…With these information, we analyzed the effect of alcohol on TGFβR1 and showed that alcohol induces TGFβR1 expression in lung fibroblasts and mouse lung while alcohol did not affect TGFβR2 expression in our experimental model (data not shown). This data is similar to the work published by Zhou et al showing that alcohol upregulated TGFβR1 expression in mouse hippocampus [28]. However, the mechanism by which alcohol regulates TGFβR1 is to be elucidated.…”

Section: Discussionsupporting

confidence: 92%

Circular RNA RORβ regulates TGFBR1 by decoying miR-140 in alcohol-exposed lungs and fibroblasts

Sueblinvong¹,

Fan²,

Williams³

et al. 2022

Preprint

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Alcohol ingestion exaggerates transforming growth factor-beta 1 (TGFβ1) expression and signaling leading to fibroproliferation. Inhibition of TGFβ receptor type 1 (TGFβR1) mitigates the effect of TGFβ1 signaling. We showed that alcohol can modulate microRNA (miRNA) expressions. The mechanism by which alcohol modulates microRNA and how it ties to TGFβ1 signaling has not been well elucidated. Circular RNA (circRNAs or circ) emerges as a potential therapeutic target based on its stability, tissue specificity, and its ability to modify miRNAs. In this study, we showed that alcohol upregulates TGFβR1 and circRNA form of retinoic acid receptor-related orphan receptor beta (circ-RORβ) in lung fibroblasts (LF) and the lung. We identified miR-140 to have binding sites for both TGFβR1 3’ UTR and circ-RORβ and alcohol attenuated miR-140 expression in LF and the lung. We demonstrated that inhibition of circ-RORβ upregulated miR-140 and completely abrogated alcohol-induced miR-140 suppression. We further showed that inhibition of circ-RORβ attenuated alcohol-induced TGFβR1, fibronectin (FN1), and α-smooth muscle actin (αSMA) expressions and myofibroblast development as seen by an attenuation of αSMA stress fiber formation in LF. Taken together, these findings identify circ-RORβ-miR-140-TGFβR1 axis as a novel mechanism by which alcohol induces TGFβ1 signaling and promotes FMD.HighlightsAlcohol induces circ-RORβ expression in lung fibroblastsCirc-RORβ regulates TGFβR1 by decoying miR-140 in lung fibroblastsInhibition of Circ-RORβ restores miR-140 expressionInhibition of Circ-RORβ mitigates alcohol-mediated myofibroblast differentiationThis is the first description of circ-RORβ functional significance in lung fibroblast

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Section: Discussionsupporting

confidence: 92%

Circular RNA RORβ regulates TGFBR1 by decoying miR-140 in alcohol-exposed lungs and fibroblasts

Sueblinvong¹,

Fan²,

Williams³

et al. 2022

Preprint

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“…In contrast, haloperidol‐induced gene expression was related to inflammatory and immune pathways, with the transcriptional regulation of ion channels being a common effect of chronic clozapine and haloperidol treatment . The analysis of the network of ethanol‐responsive genes related to proinflammatory cytokine cascade indicated novel interactions between alcohol and the immune system . Finally, a substantial impact on the alterations in expression profile induced by psychotropic drugs was observed for the network of genes related to circadian rhythm (eg, Per1 , Per2 and Bmal1 ) …”

Section: Drug‐regulated Gene Expression Networkmentioning

confidence: 99%

Decoding the transcriptional programs activated by psychotropic drugs in the brain

Zygmunt

Piechota

Parkitna

et al. 2018

Genes Brain and Behavior

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Analysis of drug-induced gene expression in the brain has long held the promise of revealing the molecular mechanisms of drug actions as well as predicting their long-term clinical efficacy.However, despite some successes, this promise has yet to be fulfilled. Here, we present an overview of the current state of understanding of drug-induced gene expression in the brain and consider the obstacles to achieving a robust prediction of the properties of psychoactive compounds based on gene expression profiles. We begin with a comprehensive overview of the mechanisms controlling drug-inducible transcription and the complexity resulting from expression of noncoding RNAs and alternative gene isoforms. Particular interest is placed on studies that examine the associations within drug classes with regard to the effects on gene transcription, alterations in cell signaling and neuropharmacological drug properties. While the ability of gene expression signatures to distinguish specific clinical classes of psychotropic and addictive drugs remains unclear, some reports show that under specific constraints, drug properties can be predicted based on gene expression. Such signatures offer a simple and effective way to classify psychotropic drugs and screen novel psychoactive compounds. Finally, we note that the amount of data regarding molecular programs activated in the brain by drug treatment has grown exponentially in recent years and that future advances may therefore come in large part from integrating the currently available high-throughput data sets.

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“…PI3K-AKT plays an important role in the formation and development of depression (Gong et al, 2021). The MAPK pathway is the key pathway of in ammatory cytokine production and can regulate the expression of in ammatory genes at post-transcription level (Zhou et al, 2017). Some studies have shown that neuronal apoptosis plays an important role in the development of depression (Shen et al, 2018).…”

Section: Molecular Docking Resultsmentioning

confidence: 99%

Antidepressant mechanism of Guipi Decoction revealed by network pharmacology and molecular docking

Wei

Song

Pan

et al. 2023

Preprint

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Guipi Decoction is a famous Traditional Chinese Medicine formulae, which can be used to treat insomnia and depression. But its specific mechanism is still unclear. In this study, the active ingredients, targets and mechanisms of the Ziziphi Spinosae Semen-Poria cocos-Longan (ZPL) in Guipi Decocation was investigated by network pharmacology analysis and molecular docking. A total of 32 active ingredients, 344 intersection targets and 13 key targets were obtained. The result showed (S)-Coclaurine, coumestrol, n-trans-feruloyltyramine, ellagic acid, ellipticine and tartaric acid were the key compounds for depression. These compositions could reduce inflammatory response, inhibit pro-inflammatory cytokines, reduce neuronal apoptosis, and then modulate depression by the key targets of RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin (IL6), mitogen activated protein kinase 3 (MAPK3). Molecular docking results showed that the binding energy of n-trans-feruloyltyramine with PPARG was the lowest, -9.513 kcal/mol and the binding energy of (S)-Coclaurine and ESR1 was − 9.336. Upregulation of AKT1 gene inhibits apoptosis. Downregulation of TNF-α, MAPK and CTNNB1 genes reduces the expression of inflammatory factors and decreases the inflammatory response, which plays an important role in the treatment of depression. In conclusion, the active component of ZPL binds stably with AKT1, MAPK3, ESR1 and CTNNB1 and controlled the onset of depression by regulation of genes expression.

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The effect of alcohol on the differential expression of cluster of differentiation 14 gene, associated pathways, and genetic network

Cited by 7 publications

References 58 publications

Circular RNA RORβ regulates TGFBR1 by decoying miR-140 in alcohol-exposed lungs and fibroblasts

Circular RNA RORβ regulates TGFBR1 by decoying miR-140 in alcohol-exposed lungs and fibroblasts

Decoding the transcriptional programs activated by psychotropic drugs in the brain

Antidepressant mechanism of Guipi Decoction revealed by network pharmacology and molecular docking

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