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Review
. 2022 Apr 11:2022:7805115.
doi: 10.1155/2022/7805115. eCollection 2022.

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook

Min Pan  1 , Fengping Zhang  1 , Kai Qu  1 , Chang Liu  1   2 , Jingyao Zhang  1   2
Affiliations
Review

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook

Min Pan et al. Oxid Med Cell Longev. .

Abstract

Thioredoxin-interacting protein (TXNIP) was originally named vitamin D3 upregulated protein-1 (VDUP1) because of its ability to bind to thioredoxin (TRX) and inhibit TRX function and expression. TXNIP is an alpha-arrestin protein that is essential for redox homeostasis in the human body. TXNIP may act as a double-edged sword in the cell. The balance of TXNIP is crucial. A study has shown that TXNIP can travel between diverse intracellular locations and bind to different proteins to play different roles under oxidative stress. The primary function of TXNIP is to induce apoptosis or pyroptosis under oxidative stress. TXNIP also inhibits proliferation and migration in cancer cells, although TXNIP levels decrease, and function diminishes in various cancers. In this review, we summarized the main structure, binding proteins, pathways, and the role of TXNIP in diseases, aiming to explore the double-edged sword role of TXNIP, and expect it to be helpful for future treatment using TXNIP as a therapeutic target.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
The core pathway of TXNIP. TXNIP: thioredoxin-interacting protein; PRAP1: poly-ADP-ribose polymerase 1; H2O2: hydrogen peroxide; ROS: reactive oxygen species; TNF: tumor necrosis factor; ASK-1: apoptotic signal-regulated kinase 1; TRX1: thioredoxin 1; TXR2: thioredoxin 2; NLRP3: NOD-like receptor family protein 3; pro-caspase-1: pro-cysteinyl aspartate specific proteinase-1; ASC: apoptosis-associated speck-like protein.
Figure 2
Figure 2
The main mechanism of TXNIP in diabetes. ROS: reactive oxygen species; TXNIP: thioredoxin-interacting protein; TRX: thioredoxin; NLRP3: NOD-like receptor family protein 3; DMF: dimethyl fumarate; VEGFER2: vascular endothelial growth factor receptor 2; VEGF: vascular endothelial growth factor; DR: diabetic retinopathy; DN: diabetic nephropathy.
Figure 3
Figure 3
The main mechanism of TXNIP in cardiovascular disease.
Figure 4
Figure 4
The main mechanism of TXNIP in cancer. TXNIP: thioredoxin-interacting protein; TRAF6: TNF receptor-related factor 6; GLS1: glutaminase 1; HDAC1: histone deacetylase 1; UHRF1: ubiquitin-like PHD and ring finger domain 1; FBWT7: F-box and WD repeat domain 7; Grapgef5: circRNA rapef5; HBx: hepatitis B virus X; Ct-HBx: C-terminal truncated X protein; NF-κB: NF downstream of pattern recognition receptor-κB; NFACT2: nuclear factor of activated T cells 2; HIF1α: hypoxia-inducible factor 1α; NaBu: sodium butyrate; EMT: epithelial-mesenchymal transition; ERK: extracellular signal-regulated kinase.
Figure 5
Figure 5
The main mechanism of TXNIP in the brain and nervous system diseases. TXNIP: thioredoxin-interacting protein; TRX: thioredoxin; NLRP3: NOD-like receptor family protein 3; Nrf2: nuclear factor erythrocyte 2-related factor 2; DI-NBP: Dl-3-n-butylphthalide.
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References

    1. Chen K. S., DeLuca H. F. Isolation and characterization of a novel cDNA from HL-60 cells treated with 1,25-dihydroxyvitamin D-3. Biochimica et Biophysica Acta . 1994;1219(1):26–32. - PubMed
    1. Nishiyama A., Matsui M., Iwata S., et al. Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression. The Journal of Biological Chemistry . 1999;274(31):21645–21650. - PubMed
    1. Zhou J., Yu Q., Chng W. J. TXNIP (VDUP-1, TBP-2): a major redox regulator commonly suppressed in cancer by epigenetic mechanisms. The International Journal of Biochemistry & Cell Biology . 2011;43(12):1668–1673. doi: 10.1016/j.biocel.2011.09.005. - DOI - PubMed
    1. Ludwig D. L., Kotanides H., Le T., Chavkin D., Bohlen P., Witte L. Cloning, genetic characterization, and chromosomal mapping of the mouse VDUP1 gene. Gene . 2001;269(1-2):103–112. - PubMed
    1. Patwari P., Higgins L. J., Chutkow W. A., Yoshioka J., Lee R. T. The interaction of thioredoxin with Txnip. Evidence for formation of a mixed disulfide by disulfide exchange. The Journal of Biological Chemistry . 2006;281(31):21884–21891. - PMC - PubMed