title: Abnormal differentiation of stem cells into enteroendocrine cells in rats with DSS-induced colitis.
abstract: The present study aimed to determine whether there is an association between abnormalities in enteroendocrine cells in dextran sulfate sodium (DSS)‑induced colitis and the clonogenic and/or proliferative activities of stem cells. A total of 48 male Wistar rats were divided into four groups. Animals in the control group were provided with normal drinking water, whereas DSS colitis was induced in the remaining three groups. The rats with DSS‑induced colitis were randomized into the following three groups: i) DSS group, which received 0.5 ml 0.5% carboxymethyl cellulose (CMC; vehicle); ii) DSS‑G group, which was treated with 3-[(dodecylthiocarbonyl)-methyl]-glutarimide at 20 mg/kg body weight in 0.5% CMC; and iii) DSS‑Q group, which was treated with dehydroxymethylepoxyquinomicin at 15 mg/kg body weight in 0.5% CMC. Treatments were administered intraperitoneally twice daily for 5 days in all groups. Subsequently, tissue samples from the colon were stained with hematoxylin‑eosin, or immunostained for chromogranin A (CgA), Musashi 1 (Msi1), Math‑1, neurogenin 3 (Neurog3) and neurogenic differentiation D1 (NeuroD1). The densities of CgA, Msi1‑, Math‑1‑, Neurog3‑ and NeuroD1-immunoreactive cells were determined. DTCM‑G, and DHMEQ ameliorated the inflammation in DSS‑induced colitis. The density of CgA‑, Neurog3‑ and NeuroD1‑immunoreactive cells was significantly higher in the DSS group compared with in the control group, and the density of CgA cells was correlated with the densities of Neurog3‑ and NeuroD1-immunoreactive cells. There were no significant differences in the densities of Msi1‑ and Math‑1‑immunoreactive cells among the four experimental groups. The elevated densities of enteroendocrine cells detected in DSS‑induced colitis may be due to the increased differentiation of early enteroendocrine progenitors during secretory lineage. It is probable that the DSS‑induced inflammatory processes trigger certain signaling pathways, which control differentiation of the stem‑cell secretory lineage into mature enteroendocrine cells.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Stord Hospital, 5409 Stord, Norway.
authors.forename: Magdy
authors.initials: M
authors.lastname: El-Salhy
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University, School of Medicine, Nagakute, Aichi 480‑1195, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway.
authors.forename: Jan Gunnar
authors.initials: JG
authors.lastname: Hatlebakk
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway.
authors.forename: Odd Helge
authors.initials: OH
authors.lastname: Gilja
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology*; D003106:Colon / Q000473:pathology*; D016264:Dextran Sulfate; D019858:Enteroendocrine Cells / Q000166:cytology / Q000473:pathology*; D008297:Male; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology / Q000473:pathology*
chemical_list: D016264:Dextran Sulfate