Investigation of Musashi-1 Expressing Cells in the Murine Model of Dextran Sodium Sulfate-Induced Colitis

Abstract

Musashi-1 (Msi-1), an RNA-binding protein, had been proposed to be a specific marker for neural stem/precursor cells. Msi-1 expressing cells in the intestinal epithelium are also strongly considered as potential stem/precursor cells. To clarify the behavior of those cells in the injury or regeneration phase, we investigated Msi-1 expressing cells of intestinal mucosa in the murine model of dextran sodium sulfate (DSS)-induced colitis. Immunohistochemically, Msi-1-positive cells were found in the area just along the layer of Paneth's cells in the small intestine and in the bottom layer of crypts in the large intestine. During DSS administration, the number of PCNA-positive cells in the large intestine increased markedly. In contrast, the number of Msi-1-positive cells decreased slightly with DSS but returned to normal after DSS administration was stopped. The level of mRNA for Msi-1 was consistent with the result of immunohistochemical examinations. Conclusively, we could describe the behavior of intestinal stem/precursor cells during inflammation using Msi-1.

5-HT4Receptor-Mediated Neuroprotection and Neurogenesis in the Enteric Nervous System of Adult Mice

“…9 H ). Msi1 is a marker for stem cells in the fetal and adult CNS and intestinal epithelium (Nagata et al, 1999; Kaneko et al, 2000; Nishimura et al, 2003; Potten et al, 2003; Fukui et al, 2006). Although epithelial Msi1-labeled cells have been detected with immunocytochemistry and in situ hybridization in mouse intestinal epithelial crypts and serosa (Potten et al, 2003; May et al, 2008), this is the first report of Msi1-immunoreactive cells associated with the ENS.…”

Intestinal Stem Cells and Their Roles During Mucosal Injury and Repair

“…Despite an observed increase in proliferation during administration of DSS, Fukui demonstrated an initial decrease in the expression of the ISC marker, Musashi-1 followed by a subsequent increase during the healing or regenerative phase of the model. 43 Similarly, in a model of doxorubicin-induced intestinal injury, an initial decrease in the expression of DCAMKL1 was observed after injury, however, no significant change in Lgr5 mRNA expression was noted. 48 Interestingly, both Musashi-1 and DCAMKL1 are thought to represent markers of the +4 position, while Lgr5 clearly arises from the CBC cells, suggesting a different response to injury based on stem cell position.…”

“…Although the more rapid turnover of cells in the small intestine as compared to the large intestine leads some to hypothesize that more ISC proliferation is required in the small bowel, the mechanisms of injury repair are likely similar to the colon. 43 An expansion of crypts surrounding ulcers formed in the colon 44 as well as an increase in crypt cells staining positive for the proliferation marker, proliferating cell nuclear antigen (PCNA) 43 have been observed following induction of chemical colitis. Although much attention has been devoted to the response of mesenchymal stem cells in models of colitis, 45–47 the specific role of the intestinal stem cell in response to colitis has not been well studied (perhaps due to the prior lack of reliable markers).…”

Novel Double-negative Feedback Loop between Adenomatous Polyposis Coli and Musashi1 in Colon Epithelia

“…Msi1 2 maintains cells in a more undifferentiated state, in part, through activation of Notch signaling and cell cycle progression (9). MSI1 is expressed in the putative intestinal stem cells (10,11).…”