MicroRNA-24 inhibits serotonin reuptake transporter expression and aggravates irritable bowel syndrome

Liao, Xiujun; Mao, Weiming; Wang, Qin; Yang, Guangli; Wu, Wenjing; Shao, Shuxian

doi:10.1016/j.bbrc.2015.11.102

Cited by 70 publications

(59 citation statements)

References 34 publications

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“…It has been reported that differential expression of several miRNAs may be correlated with inflammation [29], peripheral circulation [30], immunomodulatory [31], gut microbiota [32], and other processes that are involved in the pathogenesis of IBS-D. For example, Bitar [31] found that miR-155 was expressed in the duodenal epithelium at the acute stage of cholera and could limit the innate immune response of the host, including the inflammation evoked by its own secreted factors. Mansour’s research [32] showed that decreased expression of miR-199b would lead to an increased coliform count.…”

Section: Discussionmentioning

confidence: 99%

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1

Hou

Huang

Zhu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Irritable bowel syndrome with diarrhoea (IBS-D) is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs) are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i) identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii) verify in vitro whether occludin (OCLN) and zonula occludens 1 (ZO1/TJP1) were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii) determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. Methods: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs) and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. Results: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further studies confirmed that OCLN and ZO1 were direct targets of miR-144. Additionally, intestinal hyperpermeability was enhanced by miR-144 up-regulation and attenuated by miR-144 down-regulation in IBS-D rat colonic epithelial cells. Moreover, rescue experiments showed that overexpression of OCLN and ZO1 significantly eliminated the inhibitory effect of miR-144, which showed a stronger effect on the attenuation of intestinal hyperpermeability. Conclusion: Up-regulation of miR-144 could promote intestinal hyperpermeability and impair the protective effect of the epithelial barrier by directly targeting OCLN and ZO1. miR-144 is likely a key regulator of intestinal hyperpermeability and could be a potential therapeutic target for IBS-D.

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Section: Discussionmentioning

confidence: 99%

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1

Hou

Huang

Zhu

et al. 2017

Cell Physiol Biochem

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“…They usually arise in adults in the VI th decade of life with a male predominance[11]. Some patients have associated paraneoplastic syndromes such as Cushing’s syndrome, hypercalcemia and carcinoid syndrome.…”

Section: Epidemiology and Clinical Featuresmentioning

confidence: 99%

Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology

Crippa¹,

Partelli²,

Belfiori³

et al. 2016

WJG

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Neuroendocrine carcinomas (NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.

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“…The roles of peptides and amines in IBS are extensively reviewed elsewhere (10). The best examples are serotonin and the possible role of serotonin-selective uptake transporter (36,38), the increased plasma postprandial 5-HT in IBS-D, and reduced postprandial levels in IBS-C (3). Serotonin's effects on fluid secretion and stimulation of colonic motility and tone (54) are illustrated by the protean manifestations of carcinoid…”

Section: Enteroendocrine Cell Productsmentioning

confidence: 99%

“…They are released from their producing cells in protected forms and therefore are stable for long periods in biological fluids. Table 3 summarizes the role of several miRNAs that have been reported to have actions pertinent to IBS (25,31,36,60,61,63).…”

Section: Altered Expression Of Mucosal Molecules In Ibs Pathogenesismentioning

confidence: 99%

Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions

Camilleri

Oduyebo

Halawi

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Several chemical and molecular factors in the intestine are reported to be altered and to have a potentially significant role in irritable bowel syndrome (IBS), particularly in IBS with diarrhea. These include bile acids; short-chain fatty acids; mucosal barrier proteins; mast cell products such as histamine, proteases, and tryptase; enteroendocrine cell products; and mucosal mRNAs, proteins, and microRNAs. This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS. Evidence continues to point to significant roles in pathogenesis of these chemical and molecular mechanisms, which may therefore constitute potential targets for future research and therapy. However, it is still necessary to address the interaction between these factors in the gut and to appraise how they may influence hypervigilance in the central nervous system in patients with IBS.

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MicroRNA-24 inhibits serotonin reuptake transporter expression and aggravates irritable bowel syndrome

Cited by 70 publications

References 34 publications

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1

Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology

Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions

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