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Transcription factor EB modulates the homeostasis of reactive oxygen species in intestinal epithelial cells to alleviate inflammatory bowel disease.
Zhang, Tianci; Zhang, Ruofei; Liu, Wei; Qi, Yucheng; Wang, Hongyi; Zhang, Hu; Xiao, Zhixiong; Pandol, Stephen J; Han, Yuan-Ping; Zheng, Xiaofeng.
Afiliación
  • Zhang T; Department of Endocrinology and Metabolism, Research Center for Islet Transplantation, West China Hospital, Sichuan University, Chengdu, China; The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.
  • Zhang R; The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.
  • Liu W; The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.
  • Qi Y; The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.
  • Wang H; The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.
  • Zhang H; Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
  • Xiao Z; The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.
  • Pandol SJ; Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, USA.
  • Han YP; The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.
  • Zheng X; Department of Endocrinology and Metabolism, Research Center for Islet Transplantation, West China Hospital, Sichuan University, Chengdu, China. Electronic address: xiao-feng.zheng@outlook.com.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167065, 2024 06.
Article en En | MEDLINE | ID: mdl-38342419
ABSTRACT
Transcription factor EB (TFEB), a master lysosomal biogenesis and autophagy regulator, is crucial for cellular homeostasis, and its abnormality is related to diverse inflammatory diseases. Genetic variations in autophagic genes are associated with susceptibility to inflammatory bowel disease (IBD); however, little is known about the role and mechanism of TFEB in disease pathogenesis. In this study, we found that the genetic deletion of TFEB in mouse intestinal epithelial cells (IEC) caused intestinal barrier dysfunction, leading to increased susceptibility to experimental colitis. Mechanistically, TFEB functionally protected IEC in part through peroxisome proliferator-activated receptor gamma coactivator 1alpha (TFEB-PGC1α axis) induction, which consequently suppressed reactive oxygen species. TFEB can directly regulate PGC-1α transcription to control antioxidation level. Notably, TFEB expression is impaired and downregulated in the colon tissues of IBD patients. Collectively, our results indicate that intestinal TFEB participates in oxidative stress regulation and attenuates IBD progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Especies Reactivas de Oxígeno / Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice / Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma / Homeostasis / Mucosa Intestinal Límite: Animals / Humans / Male Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Especies Reactivas de Oxígeno / Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice / Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma / Homeostasis / Mucosa Intestinal Límite: Animals / Humans / Male Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos