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.

Gastrointestinal neuroendocrine peptides/amines in inflammatory bowel disease

“…The mechanisms underlying the changes in ENS during inflammation in IBD remain unclear. However, recent studies have shed some light on the possible mechanisms of the inflammation-induced changes in the GI endocrine cells in IBD[ 258 , 270 ].…”

“…Abnormal stem cell clonogenic and differentiation activities: Each intestinal crypt contains four to six stem cells that either divide into identical new stem cells (clonogenic) or differentiate into all types of epithelial cells through a series of progenitors[ 270 - 281 ]. This differentiation into epithelial cells includes the secretory and absorptive lineages.…”

“…The secretory lineage gives rise to endocrine, goblet, and Paneth cells. The absorptive lineage results to absorptive enterocytes[ 270 - 281 ]. In rats with TNBS-induced colitis, which is an animal model of human CD, the colonic density of Musashi-1 (Musi-1) immunoreactive cells was found to be reduced[ 258 ].…”

“…The colonic neurogenin 3 (Neurog3) cell density is reduced in rats with TNBS-induced colitis, while it is increased in rats with DSS-induced colitis[ 259 , 270 ]. Neurog3 is localized in an early progenitor belonging to the secretory lineage, which contributes to the differentiation into endocrine cells[ 286 ].…”

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

“…The mechanisms underlying such abnormalities are not yet known. However, a recent study using an animal model of human UC, namely dextran sulfate sodium-induced colitis, found that the abnormalities in enteroendocrine cells strongly correlated with the abnormal differentiation progeny of stem cells (25). It has been suggested that the abnormalities in the enteroendocrine cells in this animal model are caused by an abnormal stem cell differentiation progeny toward enteroendocrine cells (25).…”