TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis

• Published in: Cell death & disease Vol. 12; no. 10; pp. 853 - 11
• Main Authors: Tian, Na, Hu, Lei, Lu, Ying, Tong, Lingfeng, Feng, Ming, Liu, Qi, Li, Yakui, Zhu, Yemin, Wu, Lifang, Ji, Yingning, Zhang, Ping, Xu, Tianle, Tong, Xuemei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.09.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/2; 38/91; 631/80/304; 631/80/82/23; 692/699/1503/257; Adenosine Triphosphate - biosynthesis; Animals; Antibodies; Apoptosis; Apoptosis - genetics; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Proliferation - genetics; Colitis; Colitis - genetics; Colitis - pathology; Colon - pathology; Energy Metabolism; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - pathology; Epithelium; Female; Gene Deletion; Gene Ontology; Glycolysis; Immunology; Inflammatory bowel disease; Inflammatory bowel diseases; Intestinal Mucosa - pathology; Intestine; Intestines - metabolism; Intestines - pathology; Ki-67 Antigen - metabolism; Life Sciences; Metabolites; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucosa; NADP - metabolism; Pentose phosphate pathway; Rectocele - pathology; Tight junctions; Transketolase; Transketolase - deficiency; Transketolase - metabolism; Up-Regulation - genetics
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04142-4

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.