Suppression of Th17 cell differentiation via sphingosine-1-phosphate receptor 2 by cinnamaldehyde can ameliorate ulcerative colitis

Qu, Shulan; Chen, Long; Wen, Xueshan; Zuo, Jian‐Ping; Wang, Xiaoyu; Yang, Ye

doi:10.1016/j.biopha.2020.111116

Cited by 21 publications

(17 citation statements)

References 72 publications

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“…Our study indicates that MIAT is a T cell activation–associated lncRNA, especially Th17 cells, and is closely associated with AF susceptibility. This corroborates a recent study that found that cinnamaldehyde can ameliorate ulcerative colitis through the suppression of Th17 cells and the regulation of MIAT (Qu et al, 2020 ). The knockdown of MIAT has been shown to alleviate the inflammatory response and reduce intracellular oxidative stress in LPS-stimulated atrial HL-1 cells (Xing et al, 2020 ) and attenuate AF and AF-induced atrial fibrosis by targeting miR-133a-3p (Yao et al, 2020 ).…”

Section: Discussionsupporting

confidence: 92%

Identifying ceRNA Networks Associated With the Susceptibility and Persistence of Atrial Fibrillation Through Weighted Gene Co-Expression Network Analysis

Liu

Bai

et al. 2021

Front. Genet.

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Background: Atrial fibrillation (AF) is the most common arrhythmia. We aimed to construct competing endogenous RNA (ceRNA) networks associated with the susceptibility and persistence of AF by applying the weighted gene co-expression network analysis (WGCNA) and prioritize key genes using the random walk with restart on multiplex networks (RWR-M) algorithm.Methods: RNA sequencing results from 235 left atrial appendage samples were downloaded from the GEO database. The top 5,000 lncRNAs/mRNAs with the highest variance were used to construct a gene co-expression network using the WGCNA method. AF susceptibility- or persistence-associated modules were identified by correlating the module eigengene with the atrial rhythm phenotype. Using a module-specific manner, ceRNA pairs of lncRNA–mRNA were predicted. The RWR-M algorithm was applied to calculate the proximity between lncRNAs and known AF protein-coding genes. Random forest classifiers, based on the expression value of key lncRNA-associated ceRNA pairs, were constructed and validated against an independent data set.Results: From the 21 identified modules, magenta and tan modules were associated with AF susceptibility, whereas turquoise and yellow modules were associated with AF persistence. ceRNA networks in magenta and tan modules were primarily involved in the inflammatory process, whereas ceRNA networks in turquoise and yellow modules were primarily associated with electrical remodeling. A total of 106 previously identified AF-associated protein-coding genes were found in the ceRNA networks, including 16 that were previously implicated in the genome-wide association study. Myocardial infarction–associated transcript (MIAT) and LINC00964 were prioritized as key lncRNAs through RWR-M. The classifiers based on their associated ceRNA pairs were able to distinguish AF from sinus rhythm with respective AUC values of 0.810 and 0.940 in the training set and 0.870 and 0.922 in the independent test set. The AF-related single-nucleotide polymorphism rs35006907 was found in the intronic region of LINC00964 and negatively regulated the LINC00964 expression.Conclusion: Our study constructed AF susceptibility- and persistence-associated ceRNA networks, linked genetics with epigenetics, identified MIAT and LINC00964 as key lncRNAs, and constructed random forest classifiers based on their associated ceRNA pairs. These results will help us to better understand the mechanisms underlying AF from the ceRNA perspective and provide candidate therapeutic and diagnostic tools.

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Section: Discussionsupporting

confidence: 92%

Identifying ceRNA Networks Associated With the Susceptibility and Persistence of Atrial Fibrillation Through Weighted Gene Co-Expression Network Analysis

Liu

Bai

et al. 2021

Front. Genet.

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“…Further, MIAT was upregulated in rats with atherosclerosis, and it aggravated the atherosclerotic damage through PI3K/Akt activation ( 40 ). On the other hand, the expression of MIAT was reduced in the colonic tissues of colitis mice, where MIAT expression was under the control of the signaling through Sphingosine 1-phosphate receptor 2 (S1P2) ( 12 ). Further work is needed to understand the function of MIAT in Th17-mediated autoimmune disease.…”

Section: Discussionmentioning

confidence: 99%

“…Enhanced MIAT expression has also been reported in lymphocytic leukemia ( 9 ) and diabetes mellitus ( 10 ). Recent studies also suggest a role of MIAT in Th17 differentiation in mice ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 96%

Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation

Khan

Kalim

et al. 2022

Front. Immunol.

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T helper 17 (Th17) cells protect against fungal and bacterial infections and are implicated in autoimmunity. Several long intergenic noncoding RNAs (lincRNA) are induced during Th17 differentiation, however, their contribution to Th17 differentiation is poorly understood. We aimed to characterize the function of the lincRNA Myocardial Infarction Associated Transcript (MIAT) during early human Th17 cell differentiation. We found MIAT to be upregulated early after induction of human Th17 cell differentiation along with an increase in the chromatin accessibility at the gene locus. STAT3, a key regulator of Th17 differentiation, directly bound to the MIAT promoter and induced its expression during the early stages of Th17 cell differentiation. MIAT resides in the nucleus and regulates the expression of several key Th17 genes, including IL17A, IL17F, CCR6 and CXCL13, possibly by altering the chromatin accessibility of key loci, including IL17A locus. Further, MIAT regulates the expression of protein kinase C alpha (PKCα), an upstream regulator of IL17A. A reanalysis of published single-cell RNA-seq data showed that MIAT was expressed in T cells from the synovium of RA patients. Our results demonstrate that MIAT contributes to human Th17 differentiation by upregulating several genes implicated in Th17 differentiation. High MIAT expression in T cells of RA patient synovia suggests a possible role of MIAT in Th17 mediated autoimmune pathologies.

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“…Although relevant functions in IBD, only chronic but not acute inflammation affect S1PR1 expression 21 . S1PR2 activity has been associated with Na + /K + ATPase inhibition responsible for diarrhea 22 , healthy epithelial barrier function 23 , and suppression of Th17 response 24 . Inflammation 25 and bacteria 26 signal through S1PR3 as has been proved in several tissues; however, there is little information about its role in IBD.…”

Section: Discussionmentioning

confidence: 99%

Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress

Martín-Hernández

Gutiérrez

González‐Prieto

et al. 2022

Sci Rep

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The chronic inflammatory process that characterizes inflammatory bowel diseases (IBD) is mainly driven by T-cell response to microbial and environmental antigens. Psychological stress is a potential trigger of clinical flares of IBD, and sphingosine-1-phosphate (S1P) is involved in T-cell recruitment. Hence, stress impact and the absence of sphingosine kinase 2 (Sphk2), an enzyme of S1P metabolism, were evaluated in the colon of mice after sub-chronic stress exposure. Here, we show that sub-chronic stress increased S1P in the mouse colon, possibly due to a decrease in its degradation enzymes and Sphk2. S1P accumulation could lead to inflammation and immune dysregulation reflected by upregulation of toll-like receptor 4 (TLR4) pathway, inhibition of anti-inflammatory mechanisms, cytokine-expression profile towards a T-helper lymphocyte 17 (Th17) polarization, plasmacytosis, decrease in IgA+ lymphoid lineage cells (CD45+)/B cells/plasmablasts, and increase in IgM+ B cells. Stress also enhanced intestinal permeability. Sphk2 knockout mice presented a cytokine-expression profile towards a boosted Th17 response, lower expression of claudin 3,4,7,8, and structural abnormalities in the colon. Intestinal pathophysiology should consider stress and S1P as modulators of the immune response. S1P-based drugs, including Sphk2 potentiation, represent a promising approach to treat IBD.

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Suppression of Th17 cell differentiation via sphingosine-1-phosphate receptor 2 by cinnamaldehyde can ameliorate ulcerative colitis

Cited by 21 publications

References 72 publications

Identifying ceRNA Networks Associated With the Susceptibility and Persistence of Atrial Fibrillation Through Weighted Gene Co-Expression Network Analysis

Identifying ceRNA Networks Associated With the Susceptibility and Persistence of Atrial Fibrillation Through Weighted Gene Co-Expression Network Analysis

Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation

Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress

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