Evidence map›Paper›PMID 25112884›Full record

ArticleGut2015

Neurotensin--regulated miR-133α is involved in proinflammatory signalling in human colonic epithelial cells and in experimental colitis.

Ivy Ka Man Law, Kyriaki Bakirtzi, Christos Polytarchou, Angelos Oikonomopoulos, Daniel Hommes, Dimitrios Iliopoulos, Charalabos Pothoulakis

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.6field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 51 citations in OpenAlex.

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  14. Beneficial Effects of Neurotensin in Murine Model of Hapten-Induced Asthma.International journal of molecular sciences · 2019
    Article
  15. Review
  16. Article
  17. The emerging role of lncRNAs in inflammatory bowel disease.Experimental & molecular medicine · 2018
    Review
  18. Article
  19. Article
  20. Functional role and therapeutic targeting of microRNAs in inflammatory bowel disease.American journal of physiology. Gastrointestinal and liver physiology · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Ivy Ka Man LawInflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Kyriaki BakirtziInflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Christos PolytarchouCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Angelos OikonomopoulosInflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Daniel HommesInflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Dimitrios IliopoulosCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Charalabos PothoulakisInflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
University of California, Los Angeles · USCenter for Systems Biology · US

Funding

Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Women's Health and Functional Visceral Disorders CenterP50DK064539 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYER, EMERAN A · 2002 to 2017
$17.5M
Mechanisms of Neurotensin in Intestinal InflammationR01DK060729 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI POTHOULAKIS, CHARALABOS · 2002 to 2017
$5.0M
NIDDK NIH HHS DK60729NIDDK NIH HHS P30 DK041301NIDDK NIH HHS P50 DK064539NIDDK NIH HHS R01 DK060729PHS HHS NIDDK P50 DK 64539
6 · The paper itself

Abstract

objectiveNeurotensin (NT) mediates colonic inflammation through its receptor neurotensin receptor 1 (NTR1). NT stimulates miR-133α expression in colonic epithelial cells. We investigated the role of miR-133α in NT-associated colonic inflammation in vitro and in vivo.

designmiR-133α and aftiphilin (AFTPH) levels were measured by quantitative PCR. Antisense (as)-miR-133α was administrated intracolonicaly prior to induction of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis and dextran sodium sulfate (DSS)-induced colitis. The effect of AFTPH was examined by gene silencing in vitro.

resultsNT increased miR-133α levels in NCM-460 overexpressing NTR1 (NCM460-NTR1) and HCT-116 cells. NT-induced p38, ERK1/2, c-Jun, and NF-κB activation, as well as IL-6, IL-8 and IL-1β messenger RNA (mRNA) expression in NCM-460-NTR1 cells were reduced in miR-133α-silenced cells, while overexpression of miR-133α reversed these effects. MiR-133α levels were increased in TNBS (2 day) and DSS (5 day) colitis, while NTR1 deficient DSS-exposed mice had reduced miR-133α levels, compared to wild-type colitic mice. Intracolonic as-miR-133α attenuated several parameters of colitis as well expression of proinflammatory mediators in the colonic mucosa. In silico search coupled with qPCR identified AFTPH as a downstream target of miR-133α, while NT decreased AFTPH expression in NCM-460-NTR1 colonocytes. Gene silencing of AFTPH enhanced NT-induced proinflammatory responses and AFTPH levels were downregulated in experimental colitis. Levels of miR-133α were significantly upregulated, while AFTPH levels were downregulated in colonic biopsies of patients with ulcerative colitis compared to controls.

conclusionsNT-associated colitis and inflammatory signalling are regulated by miR-133α-AFTPH interactions. Targeting of miR-133α or AFTPH may represent a novel therapeutic approach in inflammatory bowel disease.

Indexed as

AnimalsColitisColonEpithelial CellsHCT116 CellsHumansMiceMice, KnockoutMicroRNAsNerve Tissue ProteinsNF-kappa BReceptors, NeurotensinSignal TransductionUp-RegulationMicroRNAsMirn133 microRNA, mouseNerve Tissue Proteinsneurotensin type 1 receptorNF-kappa BReceptors, NeurotensinCOLONIC DISEASESEXPERIMENTAL COLITISIBD BASIC RESEARCH

Identifiers

PMID25112884
PMCPMC4422787
OpenAlexW1977443233

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.