Enteroendocrine cells, stem cells and differentiation progenitors in rats with TNBS-induced colitis

El-Salhy,Magdy; Mazzawi,Tarek; Umezawa,Kazuo; Gilja,Odd  Helge

doi:10.3892/ijmm.2016.2787

Enteroendocrine cells, stem cells and differentiation progenitors in rats with TNBS-induced colitis

Authors:
- Magdy El-Salhy
- Tarek Mazzawi
- Kazuo Umezawa
- Odd Helge Gilja
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Affiliations: Division of Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, 5416 Stord, Norway, Division of Gastroenterology, Institute of Clinical Medicine, University of Bergen, 5020 Bergen, Norway, Department of Molecular Target Medicine, School of Aichi Medical University, School of Medicine, Nagakute, 480-1195 Aichi, Japan
Published online on: October 24, 2016 https://doi.org/10.3892/ijmm.2016.2787
Pages: 1743-1751
Copyright: © El-Salhy et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Patients with inflammatory bowel disease (IBD), as well as animal models of human IBD have abnormal enteroendocrine cells. The present study aimed to identify the possible mechanisms underlying these abnormalities. For this purpose, 40 male Wistar rats were divided into 4 groups as follows: the control group, the group with trinitrobenzene sulfonic acid (TNBS)-induced colitis with no treatment (TNBS group), the group with TNBS-induced colitis treated with 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G; an activator protein-1 inhibitor) (DTCM-G group), and the group with TNBS-induced colitis treated with dehydroxymethylepoxyquinomicin (DHMEQ; a nuclear factor-κB inhibitor) treatment (DHMEQ group). Three days following the administration of TNBS, the rats were treated as follows: those in the control and TNBS groups received 0.5 ml of the vehicle [0.5% carboxymethyl cellulose (CMC)], those in the DTCM-G group received DTCM-G at 20 mg/kg body weight in 0.5% CMC, and those in the DHMEQ group received DHMEQ at 15 mg/kg body weight in 0.5% CMC. All injections were administered intraperitoneally twice daily for 5 days. The rats were then sacrificed, and tissue samples were taken from the colon. The tissue sections were stained with hemotoxylin-eosin and immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin, pancreatic polypeptide (PP), somatostatin, Musashi1 (Msi1), Math1, Neurogenin3 (Neurog3) and NeuroD1. The staining was quantified using image analysis software. The densities of CgA-, PYY-, PP-, Msi1-, Neurog3- and NeuroD1-positive cells were significantly lower in the TNBS group than those in the control group, while those of serotonin-, oxyntomodulin- and somatostatin-positive cells were significantly higher in the TNBS group than those in the control group. Treatment with either DTCM-G or DHMEQ restored the densities of enteroendocrine cells, stem cells and their progenitors to normal levels. It was thus concluded that the abnormalities in enteroendocrine cells and stem cells and their differentiation progenitors may be caused by certain signaling substances produced under inflammatory processes, resulting in changes in hormone expression in enteroendocrine cells. These substances may also interfere with the colonogenic activity and the differentiation of the stem-cell secretory lineage into mature enteroendocrine cells.

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