Evidence map›Paper›PMID 28207769›Full record

ArticlePloS one2017

Role of glycogen synthase kinase-3β and PPAR-γ on epithelial-to-mesenchymal transition in DSS-induced colorectal fibrosis.

Jacopo Di Gregorio, Roberta Sferra, Silvia Speca, Antonella Vetuschi, Caroline Dubuquoy, Pierre Desreumaux, Simona Pompili, Loredana Cristiano, Eugenio Gaudio, Vincenzo Flati and 1 more

RetractedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

38 citing papers in PubMed, 50 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Jacopo Di GregorioDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Roberta SferraDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Silvia SpecaUniversity of Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France.
Antonella VetuschiDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Caroline DubuquoyIBD, Lille, France.
Pierre DesreumauxUniversity of Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France.
Simona PompiliDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Loredana CristianoDepartment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Eugenio GaudioDepartment of Human Anatomy, University of Rome La Sapienza, Rome, Italy.
Vincenzo FlatiDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Giovanni LatellaDepartment of Life, Health and Environmental Sciences, Gastroenterology Unit, University of L'Aquila, L'Aquila, Italy.
University of L'Aquila · ITInstitut de Biologie de Lille · FRLille Inflammation Research International Center · FRSapienza University of Rome · ITUniversité de Lille · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT).

aimTo evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis.

methodsChronic colitis and fibrosis were induced by oral administration of 2.5% DSS (w/v) for 6 weeks. GW9662 (GW), a selective PPAR-γ inhibitor, was also administered by intraperitoneal injection at the dose of 1 mg/kg/day combined with GED treatment. All drugs were administered at the beginning of the second cycle of DSS (day 12). 65 mice were randomly divided into five groups (H2O as controls n = 10, H2O+GED n = 10, DSS n = 15, DSS+GED n = 15, DSS+GED+GW n = 15). The colon was excised for macroscopic examination and histological and morphometric analyses. The level of expression of molecules involved in EMT and fibrosis, like TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, GSK-3β and PPAR-γ, was assessed by immunohistochemistry, immunofluorescence, western blot and Real Time PCR.

resultsGED improved the DSS-induced chronic colitis and fibrosis. GED was able to reduce the expression of the main fibrosis markers (α-SMA, collagen I-III and fibronectin) as well as the pivotal pro-fibrotic molecules IL-13, TGF-β and Smad3, while it increased the anti-fibrotic PPAR-γ. All these GED effects were nullified by co-administration of GW with GED. Furthermore, GED was able to normalize the expression levels of E-cadherin and β-catenin and upregulated GSK-3β, that are all known to be involved both in EMT and fibrosis.

conclusionsThe DSS-induced intestinal fibrosis was improved by the new PPAR-γ modulator GED-0507-34 Levo through the modulation of EMT mediators and pro-fibrotic molecules and through GSK-3β induction.

Indexed as

Epithelial-Mesenchymal TransitionAnimalsCells, CulturedColitisDextran SulfateFibrosisGlycogen Synthase Kinase 3 betaMiceMice, Inbred C57BLPPAR gammaRectumSignal TransductionTransforming Growth Factor betaDextran SulfateGlycogen Synthase Kinase 3 betaPPAR gammaTransforming Growth Factor beta

Identifiers

PMID28207769
PMCPMC5313173
OpenAlexW2587851375

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.