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Transcription factor TFEB cell-autonomously modulates susceptibility to intestinal epithelial cell injury in vivo.
Murano, Tatsuro; Najibi, Mehran; Paulus, Geraldine L C; Adiliaghdam, Fatemeh; Valencia-Guerrero, Aida; Selig, Martin; Wang, Xiaofei; Jeffrey, Kate; Xavier, Ramnik J; Lassen, Kara G; Irazoqui, Javier E.
Afiliación
  • Murano T; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
  • Najibi M; The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Paulus GLC; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
  • Adiliaghdam F; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
  • Valencia-Guerrero A; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
  • Selig M; The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Wang X; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
  • Jeffrey K; Department of Pathology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
  • Xavier RJ; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
  • Lassen KG; Department of Pathology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
  • Irazoqui JE; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Sci Rep ; 7(1): 13938, 2017 10 24.
Article en En | MEDLINE | ID: mdl-29066772
Understanding the transcription factors that modulate epithelial resistance to injury is necessary for understanding intestinal homeostasis and injury repair processes. Recently, transcription factor EB (TFEB) was implicated in expression of autophagy and host defense genes in nematodes and mammalian cells. However, the in vivo roles of TFEB in the mammalian intestinal epithelium were not known. Here, we used mice with a conditional deletion of Tfeb in the intestinal epithelium (Tfeb ΔIEC) to examine its importance in defense against injury. Unperturbed Tfeb ΔIEC mice exhibited grossly normal intestinal epithelia, except for a defect in Paneth cell granules. Tfeb ΔIEC mice exhibited lower levels of lipoprotein ApoA1 expression, which is downregulated in Crohn's disease patients and causally linked to colitis susceptibility. Upon environmental epithelial injury using dextran sodium sulfate (DSS), Tfeb ΔIEC mice exhibited exaggerated colitis. Thus, our study reveals that TFEB is critical for resistance to intestinal epithelial cell injury, potentially mediated by APOA1.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice / Mucosa Intestinal Límite: Animals Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice / Mucosa Intestinal Límite: Animals Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido