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Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review)

  • Authors:
    • Pai Zhang
    • Yabin Cui
    • Chunyan Liu
    • Chengji Cui
    • Shoulin Zhang
    • Yue Zhang
    • Fan Li
  • View Affiliations / Copyright

    Affiliations: College of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130117, P.R. China, Department of Nephrology, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China, Department of Nephrology, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130012, P.R. China, College of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130117, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 68
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    Published online on: December 16, 2025
       https://doi.org/10.3892/mmr.2025.13778
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Abstract

As an important clinical microvascular complication in diabetic patients, diabetic kidney disease (DKD) exhibits cardinal symptoms such as edema, proteinuria and unceasing reduction of renal function, and endoplasmic reticulum (ER) stress (ERS) profoundly affects its pathological course. ERS is triggered by an imbalance of ER homeostasis, which activates the three classical pathways of the unfolded protein response, including the PKR‑like ER kinase, inositol‑requiring enzyme 1α and activating transcription factor 6 pathways, to restore homeostasis. However, sustained ERS leads to apoptosis and inflammatory responses that accelerate kidney injury. Podocyte injury, renal tubular dysfunction and extracellular matrix deposition induced by ERS collectively drive the progression of DKD. The present review offer novel perspectives on potential clinical interventions for patients with DKD.
View Figures

Figure 1

ERS mechanisms. Stressors or
disease-causing factors trigger the accumulation of misfolded
proteins within the ER. This activates transcription of nuclear
genes via IRE1α, PERK, and ATF6-initiating the UPR to counteract
ERS. ATF, activating transcription factor; eIF2, eukaryotic
initiation factor 2; ERS, endoplasmic reticulum stress; IRE1α,
inositol-requiring enzyme 1α; P-, phosphorylated; PERK, PKR-like ER
kinase; TRAF2, tumor necrosis factor receptor-associated factor 2;
UPR, unfolded protein response; XBP1, X-box binding protein 1.

Figure 2

Renal endoplasmic reticulum stress
pathway in diabetic kidney disease. ATF, activating transcription
factor; eIF2α, eukaryotic initiation factor 2α; GADD34, growth
arrest and DNA-damage-inducible 34; IRE1, inositol-requiring enzyme
1; PERK, PKR-like ER kinase; ROS, reactive oxygen species. The
apoptosis pathway induces cell death via the Perk-CHOP, Caspase-12,
and JNK branches; on the right is the autophagy pathway, which
regulates cellular autophagy via the Perk/eIF2α, IRE1, and
Ca2+ branches. Different line colours carry no distinct
meaning; they are solely intended to enable readers to discern the
status of the passageway more clearly.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang P, Cui Y, Liu C, Cui C, Zhang S, Zhang Y and Li F: Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review). Mol Med Rep 33: 68, 2026.
APA
Zhang, P., Cui, Y., Liu, C., Cui, C., Zhang, S., Zhang, Y., & Li, F. (2026). Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review). Molecular Medicine Reports, 33, 68. https://doi.org/10.3892/mmr.2025.13778
MLA
Zhang, P., Cui, Y., Liu, C., Cui, C., Zhang, S., Zhang, Y., Li, F."Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review)". Molecular Medicine Reports 33.2 (2026): 68.
Chicago
Zhang, P., Cui, Y., Liu, C., Cui, C., Zhang, S., Zhang, Y., Li, F."Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review)". Molecular Medicine Reports 33, no. 2 (2026): 68. https://doi.org/10.3892/mmr.2025.13778
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang P, Cui Y, Liu C, Cui C, Zhang S, Zhang Y and Li F: Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review). Mol Med Rep 33: 68, 2026.
APA
Zhang, P., Cui, Y., Liu, C., Cui, C., Zhang, S., Zhang, Y., & Li, F. (2026). Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review). Molecular Medicine Reports, 33, 68. https://doi.org/10.3892/mmr.2025.13778
MLA
Zhang, P., Cui, Y., Liu, C., Cui, C., Zhang, S., Zhang, Y., Li, F."Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review)". Molecular Medicine Reports 33.2 (2026): 68.
Chicago
Zhang, P., Cui, Y., Liu, C., Cui, C., Zhang, S., Zhang, Y., Li, F."Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review)". Molecular Medicine Reports 33, no. 2 (2026): 68. https://doi.org/10.3892/mmr.2025.13778
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