Evidence map›Paper›PMID 26645045›Full record

ArticleCellular and molecular gastroenterology and hepatology2015

Identification of a novel substance P (SP)-neurokinin-1 receptor (NK-1R) microRNA-221-5p inflammatory network in human colonic epithelial cells.

Kai Fang, Aristea Sideri, Ivy Ka Man Law, Kyriaki Bakirtzi, Christos Polytarchou, Dimitrios Iliopoulos, Charalabos Pothoulakis

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 33% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. MiR-21 in Substance P-induced exosomes promotes cell proliferation and migration in human colonic epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2019
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Role of G protein-coupled receptors-microRNA interactions in gastrointestinal pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017
    Review
  15. Article
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 1 institution in 1 country.

Kai FangInflammatory Bowel Disease Center, David Geffen School of Medicine at UCLA.
Aristea SideriInflammatory Bowel Disease Center, David Geffen School of Medicine at UCLA.
Ivy Ka Man LawInflammatory Bowel Disease Center, David Geffen School of Medicine at UCLA.
Kyriaki BakirtziInflammatory Bowel Disease Center, David Geffen School of Medicine at UCLA.
Christos PolytarchouCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine at UCLA.
Dimitrios IliopoulosCenter for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine at UCLA.
Charalabos PothoulakisInflammatory Bowel Disease Center, David Geffen School of Medicine at UCLA.
University of California, Los Angeles · 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
SUBSTANCE P AND INTESTINAL INFLAMMATIONR01DK047343 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI POTHOULAKIS, CHARALABOS · 1994 to 2014
$4.2M
NIDDK NIH HHS P30 DK041301NIDDK NIH HHS P50 DK064539NIDDK NIH HHS R01 DK047343NIDDK NIH HHS R01 DK060729
6 · The paper itself

Abstract

BACKGROUND &

aimsSubstance P (SP), a neuropeptide member of the tachykinin family, plays a critical role in colitis. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression. However, whether SP modulates expression of microRNAs in human colonic epithelial cells remains unknown.

methodsWe performed microRNA profiling analysis of SP-stimulated human colonic epithelial NCM460 cells overexpressing neurokinin-1 receptor (NCM460-NK-1R). Targets of SP-regulated microRNAs were validated by real time polymerase chain reaction (RT-PCR). Functions of miRNAs were tested in NCM460-NK-1R cells and the TNBS and DSS models of colitis.

resultsSP stimulated differential expression of 29 microRNAs, including miR-221-5p, the highest up regulated miR (by 12.6-fold) upon SP stimulation. Bioinformatic and luciferase reporter analyses identified interleukin 6 receptor (IL-6R) mRNA as a direct target of miR-221-5p in NCM460 cells. Accordingly, SP exposure of NCM460-NK-1R cells increased IL-6R mRNA expression, while overexpression of miR-221-5p reduced IL-6R expression. NF-κB and JNK inhibition decreased SP-induced miR-221-5p expression. MiR-221-5p expression was increased in both TNBS- and DSS-induced colitis and colonic biopsies from Ulcerative Colitis, but not Crohn's Disease subjects, compared to controls. In mice, intracolonic administration of a miR-221-5p chemical inhibitor, exacerbated TNBS-and DSS-induced colitis, and increased colonic TNF-α, Cxcl10, and Col2 α 1 mRNA expression.

conclusionsOur results reveal a novel NK-1R-miR-221-5p-IL-6R network that protects from colitis. The use of miR-221-5p mimics may be a promising approach for colitis treatment.

Indexed as

colitisinflammationmicroRNASP

Identifiers

PMID26645045
PMCPMC4669978
OpenAlexW1580864846

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.