Abstract
Musashi-1 (Msi-1), a mammalian neural RNA-binding protein, has been found to play important roles in the maintenance of stem cell states and differentiation in neural stem cells and mouse intestinal cells. We explored Msi-1 expression and its potential implications in the human stomach. Reverse transcription-PCR revealed that Msi-1 levels were significantly higher in the corpus than in antrum in Helicobacter pylori (Hp)-infected patients (n = 49) (P < 0.00001) in paired biopsy samples, whereas they were low and comparable at these two sites in Hp-negative patients (n = 31). Msi-1 levels were significantly higher in the Hp-infected corpus (n = 107) than in the Hp-negative corpus (n = 69) (P < 0.00000001). Immunohistochemistry and in situ hybridization demonstrated that Msi-1 was expressed at the base and neck/isthmus region of the fundic glands and partly co-expressed in Ki-67-positive cells in the corpus and antrum. Msi-1 levels correlated with Hp density (P < 0.05). Based on these results, we conclude that Hp infection strongly induces Msi-1 in the corpus. Given its expression in dividing cells, Msi-1 may modulate the state of gastric progenitor cells.
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Okabe M, Imai T, Kurusu M, Hiromi Y, Okono H (2001) Translational repression determines a neuronal potential in Drosophila asymmetric cell division. Nature 411:94–98
Nakamura M, Okano H, Blendy JA, Montell C (1994) Musashi-1, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron 13:67–81
Sakakibara S, Okano H (1997) Expression of neural RNA-binding proteins in the postnatal CNS stem cell. J Neurosci 17:8300–8312
Kaneko Y, Sakakibara S, Imai T, Suzuki A, Nakamura Y, Sawamoto K, Ogawa Y, Toyama Y, Miyata T, Okano H (2000) Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev Neurosci 22:139–153
Sakakibara S, Nakamura Y, Yoshida T, Shibata S, Koike M, Takano H, Ueda S, Uchiyama Y, Noda T, Okano H (2002) RNA-binding protein Musashi-1 family: Roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation. Proc Natl Acad Sci USA 99:15194–15199
Okano H, Kawahara H, Toriya M, Nakao K, Shibata S, Imai T (2005) Function of RNA binding protein Musashi-1 in stem cells. Exp Cell Res 306:349–356
Imai T, Tokunaga A, Yoshida T, Hashimoto T, Mikoshiba K, Weinmaster G, Nakafuku M, Okano H (2001) The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA. Mol Cell Biol 21:3888–3900
Sugiyama-Nakagiri Y, Akiyama M, Shibata S, Okano H, Shimizu H (2006) Expression of RNA-binding protein Musashi in hair follicle development and hair cycle progression. Am J Pathol 168:80–92
Okano H, Imai T, Okabe M (2002) Musashi: a translational regulator of cell fate. J Cell Sci 115:1355–1359
Potten CS, Booth C, Tudmor GL, Booth D, Brady G, Hurley P, Ashton G, Clarke R, Sakakibara S, Okano H (2003) Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation 71:28–41
Booth C, Potten CS (2000) Gut instincts: thoughts on intestinal epithelial stem cells. J Clin Invest 105:1493–1499
Kayahara T, Sawada M, Takaishi S, Fukui H, Seno H, Fukuzawa H, Suzuki K, Hiai H, Kageyama R, Okano H, Chiba T (2003) 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
Nishimura S, Wakabayashi N, Toyoda K, Kashima K, Mitsufuji S (2003) Expression of Musashi-1 in human normal colon crypt cells: a possible stem cell marker of human colon epithelium. Dig Dis Sci 48:1523–1529
Sakatani T, Kaneda A, Iacobuzio-Donahue CA, Carter MG., de Boom Witzel S, Okano H, Ko MS, Ohlsson R, Longo DL, Feinberg AP (2005) Loss of imprinting of Igf2 alter intestinal maturation and tumorigenesis in mice. Science 307:1976–1978
Ishizuya-Oka A, Shimizu K, Sakakibara S, Okano H, Ueda S (2003) Thyroid hormone-upregulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling. J Cell Sci 116:3157–3164
Asai R, Okano H, Yasugi S (2005) Correlation between Msuashi-1 and c-hairy-1 expression and cell proliferation activity in the developing intestine and stomach of both chicken and mouse. Dev Growth Diff 47:501–510
Nagata H, Akiba Y, Suzuki H, Okano H, Hibi T (2006) Expression of Musashi-1 in the rat stomach and changes during mucosal injury and restitution. FEBS Lett 580:27–33
Akasaka Y, Saikawa Y, Fujita K, Kubota T, Ishikawa Y, Fujimoto A, Ishii T, Okano H, Kitajima M (2005) 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
Toda M, Iizuka Y, Yu W, Imai T, Ikeda E, Yoshida K, Kawase T, Kawakami Y, Okano H, Uyemura K (2001) Expression of the neural RNA-binding protein Musashi1 in human gliomas. Glia 34:1–7
Karam SM, Straiton T, Hassan WM, Leblond CP (2003) Defining epithelial cell progenitors in the human oxyntic mucosa. Stem Cells 21:322–336
Karam SM, Leblond CP (1993) Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell. Anat Rec 236:259–279
Blaser MJ, Atherton JC (2004) Helicobacter pylori persistence: biology and disease. J Clin Invest 113:321–333
Shu HJ, Saito T, Watanabe H, Ito J, Takeda H, Okano H, Kawata S (2002) Expression of the Musahi1 gene encoding the RNA-binding protein in human hepatoma cell lines. Biochem Biophys Res Commun 293:150–154
Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis. Houston 1994. Am J Surg Pathol 20:1161–1181
Petersen AM, Krogfelt KA (2003) Helicobacter pylori: an invading microorganism? A review. FEMS Immunol Med Microbiol 36:117–126
Oh JD, Karam SM, Gordon JI (2005) Intracellular Helicobacter pylori in gastric epithelial progenitors. Proc Natl Acad Sci USA 102:5186–5191
Nomura S, Esumi H, Job C, Tan SS (1998) Lineage and clonal development of gastric glands. Dev Biol 204:124–135
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This study was in part supported by the grants in aid from Japan Society for Promotion of Sciences.
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Murata, H., Tsuji, S., Tsujii, M. et al. Helicobacter Pylori Infection Induces Candidate Stem Cell Marker Musashi-1 in the Human Gastric Epithelium. Dig Dis Sci 53, 363–369 (2008). https://doi.org/10.1007/s10620-007-9858-5
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DOI: https://doi.org/10.1007/s10620-007-9858-5