title: Musashi-1 post-transcriptionally enhances phosphotyrosine-binding domain-containing m-Numb protein expression in regenerating gastric mucosa.
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 H(2)O(2)-induced cell death than control cells.
  
  
  CONCLUSIONS
  Msi1-dependent post-transcriptional enhancement of m-Numb is crucial in gastric epithelial regeneration.
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors: Tetsufumi
authors: T
authors: Takahashi
authors: Hidekazu
authors: H
authors: Suzuki
authors: Takao
authors: T
authors: Imai
authors: Shinsuke
authors: S
authors: Shibata
authors: Yoshiaki
authors: Y
authors: Tabuchi
authors: Kanji
authors: K
authors: Tsuchimoto
authors: Hideyuki
authors: H
authors: Okano
authors: Toshifumi
authors: T
authors: Hibi
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D002057:Burns, Chemical / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000293:injuries / Q000378:metabolism*; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D019000:Phosphotyrosine / Q000737:chemistry / Q000235:genetics; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D062326:Re-Epithelialization / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; C104786:Msi1h protein, mouse; C491054:Mt2 protein, mouse; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; C504399:Psca protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D019000:Phosphotyrosine; D000431:Ethanol; D008668:Metallothionein; D006861:Hydrogen Peroxide