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TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis.

ABSTRACT: Inflammatory bowel disease (IBD) has a close association with transketolase (TKT) that links glycolysis and the pentose phosphate pathway (PPP). However, how TKT functions in the intestinal epithelium remains to be elucidated. To address this question, we specifically delete TKT in intestinal epithelial cells (IECs). IEC TKT-deficient mice are growth retarded and suffer from spontaneous colitis. TKT ablation brings about striking alterations of the intestine, including extensive mucosal erosion, aberrant tight junctions, impaired barrier function, and increased inflammatory cell infiltration. Mechanistically, TKT deficiency significantly accumulates PPP metabolites and decreases glycolytic metabolites, thereby reducing ATP production, which results in excessive apoptosis and defective intestinal barrier. Therefore, our data demonstrate that TKT serves as an essential guardian of intestinal integrity and barrier function as well as a potential therapeutic target for intestinal disorders.

SUBMITTER: Tian N

PROVIDER: S-EPMC8448773 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis.

Tian Na N Hu Lei L Lu Ying Y Tong Lingfeng L Feng Ming M Liu Qi Q Li Yakui Y Zhu Yemin Y Wu Lifang L Ji Yingning Y Zhang Ping P Xu Tianle T Tong Xuemei X

Cell death & disease 20210917 10

Inflammatory bowel disease (IBD) has a close association with transketolase (TKT) that links glycolysis and the pentose phosphate pathway (PPP). However, how TKT functions in the intestinal epithelium remains to be elucidated. To address this question, we specifically delete TKT in intestinal epithelial cells (IECs). IEC TKT-deficient mice are growth retarded and suffer from spontaneous colitis. TKT ablation brings about striking alterations of the intestine, including extensive mucosal erosion, ...[more]

PMID: 34535624

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TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis.

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TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis.

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