Summary of project PR002830
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002830. The data can be accessed directly via it's Project DOI: 10.21228/M8VG27 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002830 |
| Project DOI: | doi: 10.21228/M8VG27 |
| Project Title: | TIGAR Regulates Intestinal Mucus Barrier Integrity by Inhibiting Lactylation of G6PD/6PGD in Ulcerative Colitis |
| Project Summary: | Oxidative stress and metabolic dysregulation in goblet cells represent significant contributors to the pathogenesis of ulcerative colitis (UC). TIGAR (TP53-induced glycolysis and apoptosis regulator) plays a critical role as a metabolic regulatory enzyme by promoting NADPH synthesis, thereby counteracting oxidative stress. However, the precise mechanisms through which TIGAR regulates NADPH synthesis and its impact on UC remain incompletely understood. Here, we demonstrate that TIGAR inhibits the lactylation of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), both pivotal enzymes in the NADPH biosynthesis pathway, hence preserving their enzymatic activities. We further identify specific lactylation sites at lysine 432 (K432) in G6PD and lysine 38 (K38) in 6PGD. Lactylation modifications impact the formation of G6PD homodimers and the binding of 6PGD with NADP+. In male UC mice, persistently low TIGAR expression results in elevated lactic acid levels, which enhance the lactylation of G6PD and 6PGD, inhibit NADPH synthesis, and exacerbate oxidative stress in goblet cells. Consequently, these alterations lead to a reduction in thioredoxin 1 (Trx1) reductase activity, inducing S-nitrosylation of anterior gradient homolog 2 (AGR2), a key enzyme involved in MUC2 modification, thus impeding mature MUC2 production and compromising the integrity of the intestinal mucus barrier. Overall, our study elucidates the critical mechanisms by which TIGAR regulates NADPH synthesis, provides novel insights into how TIGAR maintains cellular redox homeostasis, and offers experimental evidence for considering TIGAR as a potential target for UC therapy. |
| Institute: | Southwest Hospital, Third Military Medical University |
| Department: | Clinical Medical Research Center |
| Laboratory: | Clinical Medical Research Center |
| Last Name: | Su |
| First Name: | Sen |
| Address: | Gaotanyan Street 30, Shapingba District, Chongqing, Chongqing, 400038, China |
| Email: | 1441suse@163.com |
| Phone: | 0086015023551789 |
Summary of all studies in project PR002830
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004490 | Comparative Untargeted Metabolomics of TIGAR-Knockout and Control HIEC-6 cells | Homo sapiens | Southwest Hospital, Third Military Medical University | MS | 2026-01-02 | 1 | 12 | Uploaded data (443M)* |
| ST004491 | In Vivo Metabolic Flux Analysis of Glycolysis and the Pentose Phosphate Pathway Using U-¹³C-Glucose Stable Isotope Tracing | Mus musculus | Southwest Hospital, Third Military Medical University | MS | 2026-01-02 | 1 | 16 | Uploaded data (414.4M)* |
| ST004492 | Metabolic Flux Analysis of Glycolysis and the Pentose Phosphate Pathway Using U-¹³C-Glucose Stable Isotope Tracing in WT type and TIGAR-knockout HIEC-6 cells | Homo sapiens | Southwest Hospital, Third Military Medical University | MS | 2026-01-02 | 1 | 40 | Uploaded data (638M)* |
| ST004493 | Comparative Untargeted Metabolomics of TIGAR-Knockout and Control HT29 CL.16E Cells | Homo sapiens | Southwest Hospital, Third Military Medical University | MS | 2026-01-02 | 1 | 6 | Uploaded data (233.8M)* |
| ST004494 | Metabolic Flux Analysis of Glycolysis and the Pentose Phosphate Pathway Using U-¹³C-Glucose Stable Isotope Tracing in Wild-type and sgTIGAR HT-29 Cl.16E Cells | Homo sapiens | Southwest Hospital, Third Military Medical University | MS | 2026-01-02 | 1 | 40 | Uploaded data (803M)* |
| ST004495 | The colon tissues from TIGARf/f mice,DSS-induced TIGARf/f mice,TIGARf/fVil1-Cre mice and DSS-induced TIGARf/fVil1-Cre mice | Mus musculus | Southwest Hospital, Third Military Medical University | MS | 2026-01-02 | 1 | 12 | Uploaded data (389.5M)* |
| ST004496 | Untargeted metabolomics of the colon tissues from TIGARf/f mice and TIGARf/fVil1-Cre mice | Mus musculus | Southwest Hospital, Third Military Medical University | MS | 2026-01-06 | 1 | 6 | Uploaded data (165.6M)* |
