MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats

Huang

Zhu

et al. 2020

Preprint

Self Cite

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.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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

Huang

Zhu

et al. 2020

Preprint

Self Cite

“…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 ]. Our previous studies also have proved that miR-144 and miR-200 by binding to specific target mRNA play vital roles in IBS-D rats [ 22 , 23 ]. However, the study on lncRNAs and circRNAs in IBS-D is as yet scarce.…”

Section: Discussionmentioning

confidence: 99%

“…More and more studies have given insights into the indispensable roles of ncRNAs played in the cellular process [ 19 ], tumorigenesis [ 20 ], inflammatory regulation [ 21 ], and so on. Our previous studies also have reported that microRNA-144 and microRNA-200a are involved in intestinal permeability and visceral hyperalgesia separately by binding to specific target mRNA in IBS-D rats [ 22 , 23 ]. However, exploration about ncRNAs for IBS-D is still negligible.…”

Section: Introductionmentioning

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

Huang

Zhu

et al. 2020

Trials

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

“…The abnormal increase of visceral sensitivity may cause gastrointestinal dysfunction, and visceral hypersensitivity is thought to be an important pathophysiological factor . Diarrhea‐predominant IBS (IBS‐D), the largest sub‐category of IBS, can cause visceral pain, changed bowel habits, and bloating under normal biochemistry or anatomy . The treatments of IBS‐D include fiber supplements, probiotics, antidepressants, and a 5‐hydroxytryptophan 3 receptor antagonist, but those treatments are not so effective .…”

Section: Introductionmentioning

confidence: 99%

microRNA‐495 reduces visceral sensitivity in mice with diarrhea‐predominant irritable bowel syndrome through suppression of the PI3K/AKT signaling pathway via PKIB

Fei

2020

IUBMB Life

Diarrhea‐predominant irritable bowel syndrome (IBS‐D) is one of the most common gastrointestinal disorders in the world, lacking effective therapies. The crucial roles of microRNAs (miRNAs) in IBS‐D have attracted increasing attention. The aim of this study is to investigate the effects of miR‐495 on the visceral sensitivity of the IBS‐D through the PI3K/AKT signaling pathway by targeting PKIB. Microarray data analysis was employed to screen the differentially expressed genes related to IBS‐D and regulatory miRNAs. Then, mice were perfused with acetic acid into the rectum to establish the IBS‐D model. Next, PKIB expression was measured in IBS‐D mice. Additionally, model mice were injected with a series of adenovirus vector to investigate the influence of miR‐495 on visceral sensitivity and rectal function in IBS‐D mice with the involvement of PKIB and PI3K/AKT signaling pathway. The IBS‐D mouse model was successfully established. PKIB was the target gene of miR‐495, and highly expressed in mice with IBS‐D. Silencing PKIB reduced visceral sensitivity in mice with IBS‐D, and overexpression of miR‐495 decreased visceral sensitivity in mice with IBS‐D by inhibiting PKIB. Moreover, miR‐495 upregulation inhibited PI3K/AKT signaling pathway through downregulating PKIB. To sum up, this study reveals that miR‐495 upregulation can reduce visceral sensitivity in IBS‐D via inhibition of PI3K/AKT signaling pathway by targeting PKIB. It suggests that miR‐495 presents a potential target for IBS‐D therapy.