Density of Musashi‑1‑positive stem cells in the stomach of patients with irritable bowel syndrome

El‑Salhy,Magdy; Hausken,Trygve; Hatlebakk,Jan   Gunnar

doi:10.3892/mmr.2020.11412

Density of Musashi‑1‑positive stem cells in the stomach of patients with irritable bowel syndrome

Authors:
- Magdy El‑Salhy
- Trygve Hausken
- Jan Gunnar Hatlebakk
View Affiliations

Affiliations: Section for Gastroenterology, Department of Medicine, Stord Hospital, 5416 Stord, Norway, Department of Clinical Medicine, University of Bergen, 5020 Bergen; 3National Centre for Functional Gastrointestinal Disorders, 5021 Bergen, Norway
Published online on: August 4, 2020 https://doi.org/10.3892/mmr.2020.11412
Pages: 3135-3140
Copyright: © El‑Salhy et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Irritable bowel syndrome (IBS) affects ~12% of the global population. Although the etiology of IBS is not completely understood, several factors are known to serve a pivotal role in its pathophysiology, including genetic factors, diet, the intestinal microbiota, gastrointestinal endocrine cells and low‑grade inflammation. Musashi‑1 is expressed by stem cells and their early progeny, and is used as a stem cell marker. The low density of intestinal endocrine cells in patients with IBS is thought to be caused by decreased numbers of intestinal stem cells and their differentiation into enteroendocrine cells. The present study employed Musashi‑1 as a marker to detect stem cells in the stomach of 54 patients with IBS and 51 healthy subjects. The patients and controls underwent standard gastroscopy, and biopsy samples were taken from the corpus and antrum. Immunohistochemical staining of gastrin, somatostatin and Mushasi‑1 was carried out and semi‑quantified by computerized image analysis. The density (number of positive cells/mm2 epithelium) of gastrin‑positive cells in the controls and patients with IBS were 337.9±560 and 531.0±908 (median ± range; P<0.0001), respectively. For somatostatin‑positive cells, the density reached 364.4±526.0 in the healthy controls and 150.7±514.0 in patients with IBS (P<0.0001). The density of Musashi‑1‑positive cells was defined as the number of cells per gastric or pyloric gland neck. In the corpus, Musashi‑1‑positive cells density reached 3.0±7.0 in the corpus of the healthy controls and 3.8±7.7 in the patients with IBS. Moreover, the corresponding values in the antrum were 6.0±6.0 and 6.0±6.0, respectively. The Musashi‑1‑positive cell density did not differ significantly between the controls and patients with IBS in the corpus or antrum (P=0.4 and 0.3, respectively). These findings indicated that changes in the stomach endocrine cells observed in patients with IBS may not be explained by an abnormality in stem cells like those found in the small and large intestines of these patients.

View Figures

View References

1	El-Salhy M: Irritable bowel syndrome: Diagnosis and pathogenesis. World J Gastroenterol. 18:3135–5163. 2012. View Article : Google Scholar
2	El-Salhy M: Recent developments in the pathophysiology of irritable bowel syndrome. World J Gastroenterol. 21:7621–7636. 2015. View Article : Google Scholar : PubMed/NCBI
3	El-Salhy M, Gundersen D, Hatlebakk JG and Hausken T: Irritable bowel syndrome: Diagnosis, pathogenesis and treatment options. Nova Science Publishers, Inc.; New York: 2012
4	El-Salhy M, Hatlebakk JG, Gilja OH and Hausken T: Irritable bowel syndrome: Recent developments in diagnosis, pathophysiology, and treatment. Expert Rev Gastroenterol Hepatol. 8:435–443. 2014. View Article : Google Scholar : PubMed/NCBI
5	El-Salhy M, Gundersen D, Gilja OH, Hatlebakk JG and Hausken T: Is irritable bowel syndrome an organic disorder? World J Gastroenterol. 20:384–400. 2014. View Article : Google Scholar : PubMed/NCBI
6	El-Salhy M, Seim I, Chopin L, Gundersen D, Hatlebakk JG and Hausken T: Irritable bowel syndrome: The role of gut neuroendocrine peptides. Front Biosci (Elite Ed). 4:2783–2800. 2012.PubMed/NCBI
7	El-Salhy M and Gilja OH: Abnormalities in ileal stem, neurogenin 3, and enteroendocrine cells in patients with irritable bowel syndrome. BMC Gastroenterol. 17:902017. View Article : Google Scholar : PubMed/NCBI
8	El-Salhy M, Gilja OH, Gundersen D, Hatlebakk JG and Hausken T: Duodenal chromogranin a cell density as a biomarker for the diagnosis of irritable bowel syndrome. Gastroenterol Res Pract. 2014:4628562014. View Article : Google Scholar : PubMed/NCBI
9	El-Salhy M, Gilja OH, Gundersen D, Hatlebakk JG and Hausken T: Endocrine cells in the ileum of patients with irritable bowel syndrome. World J Gastroenterol. 20:2383–2391. 2014. View Article : Google Scholar : PubMed/NCBI
10	El-Salhy M, Gundersen D, Hatlebakk JG, Gilja OH and Hausken T: Abnormal rectal endocrine cells in patients with irritable bowel syndrome. Regul Pept. 188:60–65. 2014. View Article : Google Scholar : PubMed/NCBI
11	El-Salhy M, Gundersen D, Ostgaard H, Lomholt-Beck B, Hatlebakk JG and Hausken T: Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome. Dig Dis Sci. 57:873–878. 2012. View Article : Google Scholar : PubMed/NCBI
12	El-Salhy M, Patcharatrakul T, Hatlebakk JG, Hausken T, Gilja OH and Gonlachanvit S: Chromogranin A cell density in the large intestine of Asian and European patients with irritable bowel syndrome. Scand J Gastroenterol. 52:691–697. 2017. View Article : Google Scholar : PubMed/NCBI
13	El-Salhy M, Patcharatrakul T, Hatlebakk JG, Hausken T, Gilja OH and Gonlachanvit S: Enteroendocrine, Musashi 1 and neurogenin 3 cells in the large intestine of Thai and Norwegian patients with irritable bowel syndrome. Scand J Gastroenterol. 52:1331–1339. 2017. View Article : Google Scholar : PubMed/NCBI
14	Dizdar V, Spiller R, Singh G, Hanevik K, Gilja OH, El-Salhy M and Hausken T: Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia-induced post-infectious irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 31:883–891. 2010.PubMed/NCBI
15	El-Salhy M, Vaali K, Dizdar V and Hausken T: Abnormal small-intestinal endocrine cells in patients with irritable bowel syndrome. Dig Dis Sci. 55:3508–3513. 2010. View Article : Google Scholar : PubMed/NCBI
16	El-Salhy M, Hatlebakk JG and Hausken T: Reduction in duodenal endocrine cells in irritable bowel syndrome is associated with stem cell abnormalities. World J Gastroenterol. 21:9577–9587. 2015. View Article : Google Scholar : PubMed/NCBI
17	Montgomery RK and Breault DT: Small intestinal stem cell markers. J Anat. 213:52–58. 2008. View Article : Google Scholar : PubMed/NCBI
18	Kayahara T, Sawada M, Takaishi S, Fukui H, Seno H, Fukuzawa H, Suzuki K, Hiai H, Kageyama R, Okano H and Chiba T: Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine. FEBS Lett. 535:131–135. 2003. View Article : Google Scholar : PubMed/NCBI
19	Potten CS: Stem cells in gastrointestinal epithelium: Numbers, characteristics and death. Philos Trans R Soc Lond B Biol Sci. 353:821–830. 1998. View Article : Google Scholar : PubMed/NCBI
20	Barker N, van Oudenaarden A and Clevers H: Identifying the stem cell of the intestinal crypt: Strategies and pitfalls. Cell Stem Cell. 11:452–460. 2012. View Article : Google Scholar : PubMed/NCBI
21	Potten CS, Booth C and Pritchard DM: The intestinal epithelial stem cell: The mucosal governor. Int J Exp Pathol. 78:219–243. 1997. View Article : Google Scholar : PubMed/NCBI
22	Lee CS, Perreault N, Brestelli JE and Kaestner KH: Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity. Genes Dev. 16:1488–1497. 2002. View Article : Google Scholar : PubMed/NCBI
23	Lee CS and Kaestner KH: Clinical endocrinology and metabolism. Development of gut endocrine cells. Best Pract Res Clin Endocrinol Metab. 18:453–462. 2004. View Article : Google Scholar : PubMed/NCBI
24	El-Salhy M, Mazzawi T, Gundersen D and Hausken T: Chromogranin A cell density in the rectum of patients with irritable bowel syndrome. Mol Med Rep. 6:1223–1225. 2012. View Article : Google Scholar : PubMed/NCBI
25	El-Salhy M, Wendelbo I and Gundersen D: Reduced chromogranin A cell density in the ileum of patients with irritable bowel syndrome. Mol Med Rep. 7:1241–1244. 2013. View Article : Google Scholar : PubMed/NCBI
26	El-Salhy M, Wendelbo I and Gundersen D: Serotonin and serotonin transporter in the rectum of patients with irritable bowel disease. Mol Med Rep. 8:451–455. 2013. View Article : Google Scholar : PubMed/NCBI
27	El-Salhy M: Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome. World J Gastroenterol. 26:1427–1438. 2020. View Article : Google Scholar : PubMed/NCBI
28	El-Salhy M, Gilja OH, Gundersen D and Hausken T: Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome. World J Gastrointest Endosc. 6:176–185. 2014. View Article : Google Scholar : PubMed/NCBI
29	El-Salhy M, Gilja OH and Hausken T: Chromogranin A cells in the stomachs of patients with sporadic irritable bowel syndrome. Mol Med Rep. 10:1753–1757. 2014. View Article : Google Scholar : PubMed/NCBI
30	El-Salhy M, Gilja OH, Hatlebakk JG and Hausken T: Stomach antral endocrine cells in patients with irritable bowel syndrome. Int J Mol Med. 34:967–974. 2014. View Article : Google Scholar : PubMed/NCBI
31	El-Salhy M, Gilja OH and Hatlebakk JG: Overlapping of irritable bowel syndrome with erosive esophagitis and the performance of Rome criteria in diagnosing IBS in a clinical setting. Mol Med Rep. 20:787–794. 2019.PubMed/NCBI
32	Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F and Spiller RC: Functional bowel disorders. Gastroenterology. 130:1480–1491. 2006. View Article : Google Scholar : PubMed/NCBI
33	Han ME and Oh SO: Gastric stem cells and gastric cancer stem cells. Anat Cell Biol. 46:8–18. 2013. View Article : Google Scholar : PubMed/NCBI
34	Khurana S and Mills JC: The gastric mucosa development and differentiation. Prog Mol Biol Transl Sci. 96:93–115. 2010. View Article : Google Scholar : PubMed/NCBI
35	Akasaka Y, Saikawa Y, Fujita K, Kubota T, Ishikawa Y, Fujimoto A, Ishii T, Okano H and Kitajima M: Expression of a candidate marker for progenitor cells, Musashi-1, in the proliferative regions of human antrum and its decreased expression in intestinal metaplasia. Histopathology. 47:348–356. 2005. View Article : Google Scholar : PubMed/NCBI
36	Murata H, Tsuji S, Tsujii M, Nakamura T, Fu HY, Eguchi H, Asahi K, Okano H, Kawano S and Hayashi N: Helicobacter pylori infection induces candidate stem cell marker Musashi-1 in the human gastric epithelium. Dig Dis Sci. 53:363–369. 2008. View Article : Google Scholar : PubMed/NCBI
37	El-Salhy M, Hausken T, Gilja OH and Hatlebakk JG: The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome. Expert Rev Gastroenterol Hepatol. 11:139–148. 2017. View Article : Google Scholar : PubMed/NCBI
38	Habib AM, Richards P, Rogers GJ, Reimann F and Gribble FM: Co-localisation and secretion of glucagon-like peptide 1 and peptide YY from primary cultured human L cells. Diabetologia. 56:1413–1416. 2013. View Article : Google Scholar : PubMed/NCBI
39	El-Salhy M, Hatlebakk JG and Hausken T: Possible role of peptide YY (PYY) in the pathophysiology of irritable bowel syndrome (IBS). Neuropeptides. 79:1019732020. View Article : Google Scholar : PubMed/NCBI