Open Access

Inhibition of the SIRT1 signaling pathway exacerbates endoplasmic reticulum stress induced by renal ischemia/reperfusion injury in type 1 diabetic rats

  • Authors:
    • Jianjian Zhang
    • Lei Wang
    • Daojing Gong
    • Yuanyuan Yang
    • Xiuheng Liu
    • Zhiyuan Chen
  • View Affiliations

  • Published online on: December 18, 2019     https://doi.org/10.3892/mmr.2019.10893
  • Pages: 695-704
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Abstract

The aim of the present study was to investigate whether the diabetic kidney is more susceptible to ischemia/reperfusion (I/R) injury, and identify the potential mechanisms involved. An animal model of type 1 diabetes was created by treating rats with streptozotocin (STZ). This model was then used, along with healthy controls, to investigate the effect of diabetes mellitus (DM) on renal I/R injury. After 45 min of ischemia and 24 h of reperfusion, kidney and serum samples were acquired and used to evaluate function and histopathological injury in the kidneys. Western blotting was also used to determine the expression levels of key proteins. Rats experiencing renal I/R exhibited significant characteristics of renal dysfunction, reduced levels of Sirtuin 1 (SIRT1) protein (a key signaling protein in the kidneys), increased endoplasmic reticulum stress (ERS) and pyroptosis. Furthermore, diabetic rats exhibited further reductions in the levels of SIRT1 in response to renal I/R injury and an increase in the levels of ERS. These effects were all alleviated by the administration of a SIRT1 agonist. The present analysis revealed that the SIRT1‑mediated activation of ER stress and pyroptosis played a pivotal role in diabetic rats subjected to renal I/R injury. Downregulation of the SIRT1 signaling pathway were exacerbated in response to renal I/R injury‑induced acute kidney injury (AKI). The present data indicated that DM enhanced ER stress and increased pyroptosis by downregulating the SIRT1 signaling pathway.
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February 2020
Volume 21 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Zhang, J., Wang, L., Gong, D., Yang, Y., Liu, X., & Chen, Z. (2020). Inhibition of the SIRT1 signaling pathway exacerbates endoplasmic reticulum stress induced by renal ischemia/reperfusion injury in type 1 diabetic rats. Molecular Medicine Reports, 21, 695-704. https://doi.org/10.3892/mmr.2019.10893
MLA
Zhang, J., Wang, L., Gong, D., Yang, Y., Liu, X., Chen, Z."Inhibition of the SIRT1 signaling pathway exacerbates endoplasmic reticulum stress induced by renal ischemia/reperfusion injury in type 1 diabetic rats". Molecular Medicine Reports 21.2 (2020): 695-704.
Chicago
Zhang, J., Wang, L., Gong, D., Yang, Y., Liu, X., Chen, Z."Inhibition of the SIRT1 signaling pathway exacerbates endoplasmic reticulum stress induced by renal ischemia/reperfusion injury in type 1 diabetic rats". Molecular Medicine Reports 21, no. 2 (2020): 695-704. https://doi.org/10.3892/mmr.2019.10893