RGD Reference Report - Dietary transforming growth factor-beta 2 (TGF-beta2) supplementation reduces methotrexate-induced intestinal mucosal injury in a rat. - Rat Genome Database

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Dietary transforming growth factor-beta 2 (TGF-beta2) supplementation reduces methotrexate-induced intestinal mucosal injury in a rat.

Authors: Ben-Lulu, S  Pollak, Y  Mogilner, J  Bejar, J  G Coran, A  Sukhotnik, I 
Citation: Ben-Lulu S, etal., PLoS One. 2012;7(9):e45221. doi: 10.1371/journal.pone.0045221. Epub 2012 Sep 12.
RGD ID: 7204497
Pubmed: PMID:22984629   (View Abstract at PubMed)
PMCID: PMC3440324   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0045221   (Journal Full-text)

BACKGROUND/AIMS: Dietary supplementation with transforming growth factor-beta (TGF-beta) has been proven to minimize intestinal damage and facilitate regeneration after mucosal injury. In the present study, we evaluated the effects of oral TGF-beta2 supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat and in a cell culture model. METHODS: Caco-2 cells were treated with MTX and were incubated with increasing concentrations of TGF-beta2. Cell apoptosis was assessed using FACS analysis by annexin staining and cell viability was monitored using Trypan Blue assay. Male rats were divided into four experimental groups: Control rats, CONTR- TGF-beta rats were treated with diet enriched with TGF-beta2, MTX rats were treated with a single dose of methotrexate, and MTX- TGF-beta rats were treated with diet enriched with TGF-beta2. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined at sacrifice. Real Time PCR and Western blot were used to determine bax and bcl-2 mRNA, p-ERK, beta-catenin, IL-1B and bax protein expression. RESULTS: Treatment of MTX-pretreated Caco-2 cells with TGF-B2 resulted in increased cell viability and decreased cell apoptosis. Treatment of MTX-rats with TGF-beta2 resulted in a significant increase in bowel and mucosal weight, DNA and protein content, villus-height (ileum), crypt-depth (jejunum), decreased intestinal-injury score, decreased level of apoptosis and increased cell proliferation in jejunum and ileum compared to the untreated MTX group. MTX-TGF-beta2 rats demonstrated a lower bax mRNA and protein levels as well as increased bcl-2 mRNA levels in jejunum and ileum compared to MTX group. Treatment with TGF-beta2 also led to increased pERK, IL-1B and beta-catenin protein levels in intestinal mucosa. CONCLUSIONS: Treatment with TGF-beta2 prevents mucosal-injury, enhances p-ERK and beta-catenin induced enterocyte proliferation, inhibits enterocyte apoptosis and improves intestinal recovery following MTX-induced intestinal-mucositis in rats.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL1BHumanmucositis  ISOIl1b (Rattus norvegicus) RGD 
Il1bRatmucositis  IDA  RGD 
Il1bMousemucositis  ISOIl1b (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1b  (interleukin 1 beta)

Genes (Mus musculus)
Il1b  (interleukin 1 beta)

Genes (Homo sapiens)
IL1B  (interleukin 1 beta)


Additional Information