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Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle

  • Authors:
    • Chunmei Gu
    • Shumei Liu
    • Hongyue Wang
    • Haichuan Dou
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Endocrinology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2440-2450
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    Published online on: April 11, 2019
       https://doi.org/10.3892/ijmm.2019.4163
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Abstract

Inflammatory response serves an important role in diabetic nephropathy (DN); however, the mechanism of inflammatory response results in renal damage is not yet clear. The aim of the present study was to investigate the role of the thioredoxin interacting protein (TXNIP)/NOD‑like receptor protein 3 (NLRP3) axis‑mediated activation of NLRP3 inflammasome in DN. A diabetic rat model was induced by streptozotocin injection. Hematoxylin and eosin (H&E) staining and streptavidin‑peroxidase staining were then used to examine the kidney tissue morphology, and TXNIP and NLRP3 protein expression levels, respectively. Furthermore, RNA interference technology was applied to silence the TXNIP gene. TXNIP and NLRP3 inflammasome activation‑associated proteins and mRNAs were detected by western blot analysis and RT‑qPCR, respectively. Enzyme‑linked immunosorbent assay was also used to examine interleukin (IL)‑1 and IL‑18 expression, while flow cytometry was performed to detect reactive oxygen species production. The data revealed that TXNIP and NLRP3 were overexpressed in kidney tissue of DN rats, and the level of antioxidant genes was downregulated. It was also observed that glucose promoted TXNIP expression and activation of NLRP3 inflammasome in a time‑dependent and dose‑dependent manner, therefore promoting inflammatory responses. Silencing of TXNIP gene resulted in the downregulation of NLRP3 inflammasome activation, and inhibited the expression levels of IL‑1 and IL‑18 in a high‑glucose environment. Furthermore, low expression of TXNIP promoted the levels of antioxidant genes and reduced the ROS levels. Taken together, the high‑glucose environment was able to upregulated the level of inflammatory factors by promoting the expression of TXNIP and the activation of NLRP3 inflammasome, consequently participating in DN.
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Spandidos Publications style
Gu C, Liu S, Wang H and Dou H: Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle . Int J Mol Med 43: 2440-2450, 2019.
APA
Gu, C., Liu, S., Wang, H., & Dou, H. (2019). Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle . International Journal of Molecular Medicine, 43, 2440-2450. https://doi.org/10.3892/ijmm.2019.4163
MLA
Gu, C., Liu, S., Wang, H., Dou, H."Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle ". International Journal of Molecular Medicine 43.6 (2019): 2440-2450.
Chicago
Gu, C., Liu, S., Wang, H., Dou, H."Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle ". International Journal of Molecular Medicine 43, no. 6 (2019): 2440-2450. https://doi.org/10.3892/ijmm.2019.4163
Copy and paste a formatted citation
x
Spandidos Publications style
Gu C, Liu S, Wang H and Dou H: Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle . Int J Mol Med 43: 2440-2450, 2019.
APA
Gu, C., Liu, S., Wang, H., & Dou, H. (2019). Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle . International Journal of Molecular Medicine, 43, 2440-2450. https://doi.org/10.3892/ijmm.2019.4163
MLA
Gu, C., Liu, S., Wang, H., Dou, H."Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle ". International Journal of Molecular Medicine 43.6 (2019): 2440-2450.
Chicago
Gu, C., Liu, S., Wang, H., Dou, H."Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating NOD‑like receptor protein 3 inflammatory corpuscle ". International Journal of Molecular Medicine 43, no. 6 (2019): 2440-2450. https://doi.org/10.3892/ijmm.2019.4163
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