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Impaired Wnt/ß-catenin pathway leads to dysfunction of intestinal regeneration during necrotizing enterocolitis.
Li, Bo; Lee, Carol; Cadete, Marissa; Zhu, Haitao; Koike, Yuhki; Hock, Alison; Wu, Richard Y; Botts, Steven R; Minich, Adam; Alganabi, Mashriq; Chi, Lijun; Zani-Ruttenstock, Elke; Miyake, Hiromu; Chen, Yong; Mutanen, Annika; Ngan, Bo; Johnson-Henry, Kathene C; De Coppi, Paolo; Eaton, Simon; Määttänen, Pekka; Delgado-Olguin, Paul; Sherman, Philip M; Zani, Augusto; Pierro, Agostino.
Afiliación
  • Li B; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Lee C; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Cadete M; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Zhu H; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Koike Y; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Hock A; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Wu RY; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Botts SR; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Minich A; Department of Pediatric Surgery, Children's Hospital of Fudan University, 201102, Shanghai, China.
  • Alganabi M; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Chi L; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Zani-Ruttenstock E; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Miyake H; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Chen Y; Cell Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Mutanen A; Cell Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Ngan B; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Johnson-Henry KC; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • De Coppi P; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Eaton S; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Määttänen P; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Delgado-Olguin P; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Sherman PM; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Zani A; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
  • Pierro A; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Cell Death Dis ; 10(10): 743, 2019 10 03.
Article en En | MEDLINE | ID: mdl-31582728
ABSTRACT
Necrotizing enterocolitis (NEC) is a devastating neonatal disease characterized by acute intestinal injury. Intestinal stem cell (ISC) renewal is required for gut regeneration in response to acute injury. The Wnt/ß-catenin pathway is essential for intestinal renewal and ISC maintenance. We found that ISC expression, Wnt activity and intestinal regeneration were all decreased in both mice with experimental NEC and in infants with acute active NEC. Moreover, intestinal organoids derived from NEC-injured intestine of both mice and humans failed to maintain proliferation and presented more differentiation. Administration of Wnt7b reversed these changes and promoted growth of intestinal organoids. Additionally, administration of exogenous Wnt7b rescued intestinal injury, restored ISC, and reestablished intestinal epithelial homeostasis in mice with NEC. Our findings demonstrate that during NEC, Wnt/ß-catenin signaling is decreased, ISC activity is impaired, and intestinal regeneration is defective. Administration of Wnt resulted in the maintenance of intestinal epithelial homeostasis and avoidance of NEC intestinal injury.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Enterocolitis Necrotizante / Vía de Señalización Wnt / Intestinos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Death Dis Año: 2019 Tipo del documento: Article País de afiliación: Canadá
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Enterocolitis Necrotizante / Vía de Señalización Wnt / Intestinos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Death Dis Año: 2019 Tipo del documento: Article País de afiliación: Canadá