Transcription factor EB modulates the homeostasis of reactive oxygen species in intestinal epithelial cells to alleviate inflammatory bowel disease

Tianci Zhang; Ruofei Zhang; Wei Liu; Yucheng Qi; Hongyi Wang; Hu Zhang; Zhixiong Xiao; Stephen J Pandol; Yuan-Ping Han; Xiaofeng Zheng

doi:10.1016/j.bbadis.2024.167065

Transcription factor EB modulates the homeostasis of reactive oxygen species in intestinal epithelial cells to alleviate inflammatory bowel disease

Biochim Biophys Acta Mol Basis Dis. 2024 Feb 9;1870(5):167065. doi: 10.1016/j.bbadis.2024.167065. Online ahead of print.

Authors

Affiliations

¹ 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.
² The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.
³ Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
⁴ Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, USA.
⁵ Department of Endocrinology and Metabolism, Research Center for Islet Transplantation, West China Hospital, Sichuan University, Chengdu, China. Electronic address: xiao-feng.zheng@outlook.com.

PMID: 38342419
DOI: 10.1016/j.bbadis.2024.167065

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.

Keywords: Inflammatory bowel disease; Intestinal epithelial cell; Peroxisome proliferator-activated receptor gamma coactivator 1alpha; Reactive oxygen species; Transcription factor EB.