Evidence map›Paper›PMID 27561676›Full record

ArticleScientific reports2016

Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development.

Kazuhiko Uchiyama, Toshio Sakiyama, Takumu Hasebe, Mark W Musch, Hiroyuki Miyoshi, Yasushi Nakagawa, Tong-Chuan He, Lev Lichtenstein, Yuji Naito, Yoshito Itoh and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

20 citing papers in PubMed, 36 citations in OpenAlex.

  1. Butyrate, IL-4, and EP4 Receptors: A Triad of Colorectal Homeostasis, Protecting Against Onset of Cancer and IBD?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  2. Assessing the health of the gut microbial organ: why and how?The Journal of clinical investigation · 2025
    Article
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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

14 authors at 4 institutions in 3 countries.

Kazuhiko UchiyamaDepartment of Medicine, University of Chicago, Chicago, IL 60637; USA.
Toshio SakiyamaDepartment of Medicine, University of Chicago, Chicago, IL 60637; USA.
Takumu HasebeDepartment of Medicine, University of Chicago, Chicago, IL 60637; USA.
Mark W MuschDepartment of Medicine, University of Chicago, Chicago, IL 60637; USA.
Hiroyuki MiyoshiDepartment of Pathology, Washington University at St. Louis, St. Louis, MO, USA.
Yasushi NakagawaDepartment of Medicine, University of Chicago, Chicago, IL 60637; USA.
Tong-Chuan HeDepartment of Surgery, University of Chicago; Chicago, IL 60637; USA.
Lev LichtensteinDepartment of Medicine, University of Chicago, Chicago, IL 60637; USA.
Yuji NaitoDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566; Japan.
Yoshito ItohDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566; Japan.
Toshikazu YoshikawaDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 6028566; Japan.
Bana JabriDepartment of Medicine, University of Chicago, Chicago, IL 60637; USA.
Thaddeus StappenbeckDepartment of Pathology, Washington University at St. Louis, St. Louis, MO, USA.
Eugene B ChangDepartment of Medicine, University of Chicago, Chicago, IL 60637; USA.
University of Chicago · USKyoto Prefectural University of Medicine · JPWashington University in St. Louis · USKagoshima University · JP

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI MARK W. LINGEN · 1985 to 2026
$122.1M
ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI LIU, CAMBRIAN YANGSHAO · 1990 to 2025
$29.8M
The Role of the Gut Microbiota in Ulcerative ColitisUH3DK083993 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHANG, EUGENE B, MEYER, FOLKER · 2010 to 2012
$8.2M
Mutualistic relationship between Hsp25/27 and gut microbes as a major and essential determinant of mucosal healing and microbial fitness following intestinal injuryR01DK047722 · NIDDK · UNIVERSITY OF CHICAGO · PI CHANG, EUGENE B · 1993 to 2020
$4.3M
Cytoprotective Role of Heat Shock Proteins in IBDR37DK047722 · NIDDK · UNIVERSITY OF CHICAGO · PI CHANG, EUGENE B · 2008 to 2017
$3.8M
Dietary fat effects on gut microbes, host immune state and experimental colitisR01DK097268 · NIDDK · UNIVERSITY OF CHICAGO · PI CHANG, EUGENE B · 2012 to 2016
$2.2M
Regulation of beta-Catenin Signaling by Tyrosine PhosphorylationR01CA106569 · NCI · UNIVERSITY OF CHICAGO · PI HE, TONG-CHUAN · 2006 to 2010
$1.3M
NCI NIH HHS P30 CA014599NCI NIH HHS R01 CA106569NIDDK NIH HHS P30 DK042086NIDDK NIH HHS R01 DK047722NIDDK NIH HHS R01 DK097268NIDDK NIH HHS R37 DK047722NIDDK NIH HHS UH3 DK083993
6 · The paper itself

Abstract

Proliferation and spatial development of colonic epithelial cells are highly regulated along the crypt vertical axis, which, when perturbed, can result in aberrant growth and carcinogenesis. In this study, two key factors were identified that have important and counterbalancing roles regulating these processes: pericrypt myofibroblast-derived Wnt-5a and the microbial metabolite butyrate. Cultured YAMC cell proliferation and heat shock protein induction were analzyed after butryate, conditioned medium with Wnt5a activity, and FrzB containing conditioned medium. In vivo studies to modulate Hsp25 employed intra-colonic wall Hsp25 encoding lentivirus. To silence Wnt-5a in vivo, intra-colonic wall Wnt-5a silencing RNA was used. Wnt-5a, secreted by stromal myofibroblasts of the lower crypt, promotes proliferation through canonical β-catenin activation. Essential to this are two key requirements: (1) proteolytic conversion of the highly insoluble ~40 kD Wnt-5a protein to a soluble 36 mer amino acid peptide that activates epithelial β-catenin and cellular proliferation, and (2) the simultaneous inhibition of butyrate-induced Hsp25 by Wnt-5a which is necessary to arrest the proliferative process in the upper colonic crypt. The interplay and spatial gradients of these factors insures that crypt epithelial cell proliferation and development proceed in an orderly fashion, but with sufficient plasticity to adapt to physiological perturbations including inflammation.

Indexed as

AnimalsButyratesCell LineCell ProliferationColonEpithelial CellsHeat-Shock ProteinsIntestinal MucosaMiceMolecular ChaperonesNeoplasm ProteinsProteolysisWnt-5a ProteinButyratesHeat-Shock ProteinsHsbp1 protein, mouseMolecular ChaperonesNeoplasm ProteinsWnt-5a ProteinWnt5a protein, mouse

Identifiers

PMID27561676
PMCPMC4999796
OpenAlexW2512122274

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.