Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells

Minekazu Murayama, Ryuichi Okamoto, Kiichiro Tsuchiya, Junko Akiyama, Tetsuya Nakamura, Naoya Sakamoto, Takanori Kanai, Mamoru Watanabe

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Background: Musashi-1 (Msi-1) is a RNA-binding protein, known as a putative marker of intestinal stem cells (ISCs). However, little is known about the function of Msi-1 within human intestinal epithelial cells (IECs). Thus, the present study aimed to clarify the role of Msi-1 in differentiation and proliferation of IECs. Methods: A human intestinal epithelial cell line stably expressing Msi-1 was established. Proliferation of the established cell lines was measured by bromodeoxyuridine incorporation, whereas differentiation were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of lineage-specific genes. Activities of the Notch and Wnt pathways were examined either by reporter assays or expression of downstream target genes. The distribution of Msi-1 and PLA2G2A expression in vivo was determined by immunohistochemistry. Results: Constitutive expression of Msi-1 in IECs had no significant effect on cell proliferation, but suppressed expression of Paneth cell-specific genes, including PLA2G2A. Msi-1 appeared to suppress expression of the PLA2G2A gene at the mRNA level. Analysis of Notch and Wnt pathway activity, however, revealed no significant change upon Msi-1 expression. The expression of Msi-1 and PLA2G2A in vivo was restricted to IECs residing at the lowest part of the human intestinal crypt, but was clearly separated to within basal columnar cells or mature Paneth cells, respectively. Conclusions: Msi-1 suppresses expression of Panethcell-specific genes in IECs, presumably through a pathway independent from Notch or Wnt. These findings suggest Msi-1 is a negative regulator of Paneth cell differentiation, an may contribute to maintain the undifferentiated phenotype of ISCs.

Original languageEnglish
Pages (from-to)173-182
Number of pages10
JournalJournal of gastroenterology
Volume44
Issue number3
DOIs
Publication statusPublished - 2009 Feb 24
Externally publishedYes

Keywords

  • Intestinal epithelial cells
  • Musashi-1
  • PLAG2A
  • Paneth cells

ASJC Scopus subject areas

  • Gastroenterology

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