Regulation of Colonic Mucosal MicroRNA Expression via Multiple Targets in Visceral Hypersensitivity Rats by Tongxieyaofang

Chao, Guanqun; Wang, Yingying; Ye, Fangxu; Zhang, Shuo

doi:10.3349/ymj.2018.59.8.945

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…An experimental mouse model of IBS-D was established as per previous study ( 17 , 18 ). Then, 40 mice were randomly assigned into four groups: Control, model, miRNA-29a negative control and miRNA-29a inhibitor groups.…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of miRNA‑29a regulates intestinal barrier function in diarrhea‑predominant irritable bowel syndrome by upregulating ZO‑1 and CLDN1

et al. 2020

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Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder. MicroRNAs (miRNAs) have been identified to be involved in different physiological and pathological processes. In this study, the role of miRNA-29a in the potential mechanism underlying the function of the intestinal mucosal barrier in IBS-D was analyzed. Human intestinal mucosal epithelia from patients with IBS-D (diagnosed as meeting the Rome IV criteria) and healthy volunteers were collected. An IBS-D mouse model was established via induction with trinitro-benzene-sulfonic acid (TNBS), and the mice were injected with miRNA-29a inhibitor. Using transmission electron microscopy (TEM), the epithelial ultrastructure of the human intestinal mucosa was examined. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, the expression level of miRNA-29a was assessed. ELISA was used to analyze the activity of D-lactate (D-LA) and diamine oxidase (DAO). Through immunohistochemistry, RT-qPCR and western blotting, the expression of tight junction protein ZO-1 (ZO-1) and claudin-1 (CLDN1) was examined. In the human intestinal mucosal epithelia from patients with IBS-D, miRNA-29a was upregulated, ZO-1 and CLDN1 were downregulated, and the junctional complex (JC) was faint and discontinuous. In the IBS-D mouse model, treatment with miRNA-29a inhibitor downregulated D-LA and DAO activity, and increased the expression of ZO-1 and CLDN1 in the intestinal mucosal epithelium. In conclusion, the present study revealed that miRNA-29a is involved in the pathogenesis of IBS-D, probably by downregulating ZO-1 and CLDN1 expression, suggesting that miRNA-29a is likely to be an important regulator of intestinal barrier function and could be a possible therapeutic target for IBS-D.

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Section: Methodsmentioning

confidence: 99%

“…In total, 10 samples in each group were analyzed. (17,18). Then, 40 mice were randomly assigned into four groups: Control, model, miRNA-29a negative control and miRNA-29a inhibitor groups.…”

Section: Patients the Study Included 21 Patients With Ibs-d Admittedmentioning

confidence: 99%

Inhibition of miRNA‑29a regulates intestinal barrier function in diarrhea‑predominant irritable bowel syndrome by upregulating ZO‑1 and CLDN1

et al. 2020

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“…This trial not only explores the efficacy and safety of TXYF granule but also focuses on the whole transcriptome profiling of IBS-D and the therapeutic pathways of TXYF granule. A previous study has concluded that miRNAs play a pivotal role in the IBS rat model by utilizing liquid chip and qRT-PCR and might be the targets of TXYF in the treatment of IBS [ 33 ]. Other literatures have reported that in IBS-D patients, miR-199 and miR-29 are respectively involved in visceral pain and intestinal permeability [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Tong-Xie-Yao-Fang granule and its impact on whole transcriptome profiling in diarrhea-predominant irritable bowel syndrome patients: study protocol for a randomized controlled trial

Wang

Huang

Zhu

et al. 2020

Trials

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Background Irritable bowel syndrome (IBS) is one kind of common functional bowel disease with obscure pathogenesis, and exploration about whole transcriptome profiling in IBS-D is still negligible. Conventional medications have limited effects, which makes focus shifted to traditional Chinese medicine (TCM). Tong-Xie-Yao-Fang, as a classic herbal formula in TCM, is pretty effective and safe for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying therapeutic mechanism remains unknown. We aim to verify the efficacy and safety of TXYF granule (the formula particles mixed together) in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXYF granule based on whole transcriptome analysis. Methods/design This is a randomized, double-blind, and placebo-controlled clinical trial consisting of 2 weeks of run-in period, 12 weeks of treatment period, and 8 weeks of follow-up period. We will enroll 120 participants with IBS-D, who will be randomly assigned to the TXYF granule group and the placebo group, and recruit additional 10 healthy individuals as controls for mechanistic outcome. The two groups respectively take TXYF granule or placebo orally for treatment. The primary outcome is the response rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes include adequate relief (AR), IBS-Quality of Life Questionnaire (IBS-QOL), and long-term efficacy. Mechanistic outcome is the whole transcriptome profiling of the intestinal mucosae from IBS participants before and after the treatment and healthy individuals. Discussion This trial will prove the effectiveness and safety of TXYF granule with high-quality evidence and provide a penetrating and comprehensive perspective on the molecular mechanism of IBS-D by whole transcriptome analysis, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXYF. Trial registration Chinese Clinical Trial Registry ChiCTR-IOR-1900021785. Registered on 9 March 2019

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“…This trial not only explores the e cacy and safety of TXYF granule but also focuses on the whole transcriptome pro ling of IBS-D and the therapeutic pathways of TXYF granule. Previous study has concluded that miRNAs play a pivotal role in IBS rat model by utilizing liquid chip and qRT-PCR and might be the targets of TXYF in the treatment of IBS (33). Other literatures have reported that in IBS-D patients, miR-199 and miR-29 are respectively involved in visceral pain and intestinal permeability (34,35).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Tong-Xie-Yao-Fang Granule and its Impact on Whole Transcriptome Profiling in Diarrhea-Predominant Irritable Bowel Syndrome Patients: Study Protocol for a Randomized Controlled Trial

Liu

Wang

Huang

et al. 2020

Preprint

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Background: Irritable bowel syndrome (IBS) is one kind of common functional bowel disease with obscure pathogenesis and exploration about whole transcriptome profiling in IBS-D is still negligible. Conventional medications have limited effects, which makes focus shifted to traditional Chinese medicine (TCM). Tong-Xie-Yao-Fang, as a classic herbal formula in TCM, is pretty effective and safe for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying therapeutic mechanism remains unknown. We aim to verify the efficacy and safety of TXYF granule (the formula particles mixed together) in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXYF granule based on whole transcriptome analysis. Methods/design: This is a randomized, double-blind and placebo-controlled clinical trial consisting of 2 weeks run-in period, 12 weeks treatment period and 8 weeks follow-up period. We will enroll 120 participants with IBS-D, who will be randomly assigned to TXYF granule group and the placebo group and recruit additional 10 healthy individuals as controls for mechanistic outcome. The two groups respectively take TXYF granule or placebo orally for treatment. The primary outcome is the response rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes include adequate relief (AR), IBS-Quality of Life Questionnaire (IBS-QOL) and long-term efficacy. Mechanistic outcome is the whole transcriptome profiling of the intestinal mucosae from IBS participants before and after the treatment and healthy individuals. Discussion: This trial will prove the effectiveness and safety of TXYF granule with high-quality evidence and provide a penetrating and comprehensive perspective on the molecular mechanism of IBS-D by whole transcriptome analysis, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXYF.Trial registration: Chinese clinical trial Registry: ChiCTR-IOR-1900021785 (URL: http://www.chictr.org.cn/showproj.aspx?proj=36642).Date of registration: 9 March 2019.

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Regulation of Colonic Mucosal MicroRNA Expression via Multiple Targets in Visceral Hypersensitivity Rats by Tongxieyaofang

Cited by 6 publications

References 37 publications

Inhibition of miRNA‑29a regulates intestinal barrier function in diarrhea‑predominant irritable bowel syndrome by upregulating ZO‑1 and CLDN1

Inhibition of miRNA‑29a regulates intestinal barrier function in diarrhea‑predominant irritable bowel syndrome by upregulating ZO‑1 and CLDN1

Efficacy of Tong-Xie-Yao-Fang granule and its impact on whole transcriptome profiling in diarrhea-predominant irritable bowel syndrome patients: study protocol for a randomized controlled trial

Efficacy of Tong-Xie-Yao-Fang Granule and its Impact on Whole Transcriptome Profiling in Diarrhea-Predominant Irritable Bowel Syndrome Patients: Study Protocol for a Randomized Controlled Trial

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