Musashi-1 Post-Transcriptionally Enhances Phosphotyrosine-Binding Domain-Containing m-Numb Protein Expression in Regenerating Gastric Mucosa

Tetsufumi Takahashi, Hidekazu Suzuki, Takao Imai, Shinsuke Shibata, Yoshiaki Tabuchi, Kanji Tsuchimoto, Hideyuki Okano, Toshifumi Hibi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective: Upregulation of the RNA-binding protein Musashi-1 (Msi1) has been shown to occur in rat gastric corpus mucosa after ethanol-induced mucosal injury. However, there is no direct evidence linking Msi1 with gastric regeneration. We examined the process of tissue repair after acute gastric mucosal injury with Msi1-knock-out (KO) mice to clarify the role of Msi1 and Msi1-dependent regulation of m-Numb expression in regenerating gastric mucosa. Methods: Acute gastric injury was induced in Msi1-KO and wild-type ICR mice by administering absolute ethanol. Expression of the splicing variants of m-Numb mRNA and protein in the gastric mucosa were analyzed by quantitative RT-PCR and western blotting, respectively. Results: We demonstrated that phosphotyrosine-binding domain-containing m-Numb expression was significantly upregulated at both the mRNA and protein levels in wild-type mice at 3 h after ethanol-induced acute gastric injury. In contrast, in Msi1-KO mice, the m-Numb protein was expressed weakly, and was associated with delayed regeneration of the injured gastric mucosal epithelium. In the Msi1-KO mouse, the ratio of m-Numb mRNA to total m-Numb mRNA in the heavy polysome fractions was lower than that in the wild-type mouse. Further, we showed that m-Numb-enhancement in gastric mucous cells induced the expression of prostate stem cell antigen and metallothionein-2. Under the m-Numb enhancing condition, the gastric cells exhibited enhanced cell proliferation and were significantly more resistant to H2O2-induced cell death than control cells. Conclusions: Msi1-dependent post-transcriptional enhancement of m-Numb is crucial in gastric epithelial regeneration.

Original languageEnglish
Article numbere53540
JournalPLoS One
Volume8
Issue number1
DOIs
Publication statusPublished - 2013 Jan 4

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Phosphotyrosine
gastric mucosa
Gastric Mucosa
Stomach
stomach
protein synthesis
Messenger RNA
Ethanol
Proteins
mice
Knockout Mice
Regeneration
RNA-Binding Proteins
Metallothionein
Wounds and Injuries
Cell proliferation
Cell death
Stem cells
ethanol
Rats

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Musashi-1 Post-Transcriptionally Enhances Phosphotyrosine-Binding Domain-Containing m-Numb Protein Expression in Regenerating Gastric Mucosa. / Takahashi, Tetsufumi; Suzuki, Hidekazu; Imai, Takao; Shibata, Shinsuke; Tabuchi, Yoshiaki; Tsuchimoto, Kanji; Okano, Hideyuki; Hibi, Toshifumi.

In: PLoS One, Vol. 8, No. 1, e53540, 04.01.2013.

Research output: Contribution to journalArticle

Takahashi, Tetsufumi ; Suzuki, Hidekazu ; Imai, Takao ; Shibata, Shinsuke ; Tabuchi, Yoshiaki ; Tsuchimoto, Kanji ; Okano, Hideyuki ; Hibi, Toshifumi. / Musashi-1 Post-Transcriptionally Enhances Phosphotyrosine-Binding Domain-Containing m-Numb Protein Expression in Regenerating Gastric Mucosa. In: PLoS One. 2013 ; Vol. 8, No. 1.
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