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Li Zhou, Xin-Lei Shen, Qing-Ru Zhu, Wen-Kai Yu, Hang-Chao Li, Gang Cao, Yi-Ni Bao. Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101558
Citation: Li Zhou, Xin-Lei Shen, Qing-Ru Zhu, Wen-Kai Yu, Hang-Chao Li, Gang Cao, Yi-Ni Bao. Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101558
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Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy

doi: 10.1016/j.jpha.2026.101558

  • a. School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, 310053, China;

  • b. Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, China

Funds:

This work was financially supported by the National Natural Science Foundation of China (Grant No.: 82204625), the Natural Science Foundation of Zhejiang Province, China (Grant No.: LQ23H280013), the Chinese Medicine Research Program of Zhejiang Province, China (Grant No.: 2023ZR009), the Youth Natural Science Program of Zhejiang Chinese Medical University (Grant No.: 2025JKZKTS26), and the Integrated Traditional Chinese and Western Medicine Prevention and Treatment of Severe Hematological Diseases Heritage and Innovation Team (Grant No.: 20250701). We appreciate the great help from the Pharmaceutical Research Center and Medical Research Center, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University (Hangzhou, China). All figures, including Graphical abstract, were drawn by using BioRender.com.

  • Received Date: May 30, 2025
  • Accepted Date: Jan. 19, 2026
  • Rev Recd Date: Jan. 19, 2026
  • Available Online: Jan. 21, 2026
    Abstract
  • Diabetic nephropathy (DN), a major microvascular complication of diabetes, is the leading cause of chronic kidney disease (CKD). Oxidative stress has emerged as a central driver of DN, making its associated signaling pathways promising therapeutic targets. When reactive oxygen species (ROS) exceed the cell’s antioxidant capacity, they disrupt homeostasis and trigger inflammation, apoptosis, necrosis, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. In the kidneys, these events accelerate fibroblast activation and collagen deposition, leading to fibrosis, glomerulosclerosis, and progressive loss of function. Recent studies identify post-translational modifications (PTMs) as key regulators in this process. By altering protein structure, function, and interactions, PTMs modulate many of the pathological mechanisms underlying DN. Targeting oxidative stress pathways regulated by PTMs therefore offers a promising therapeutic approach. In this review, we first introduce the role of PTMs in DN and outline the contribution of oxidative stress to disease progression. We then examine how PTMs regulate oxidative stress pathways, highlight novel modifications with potential relevance to DN, and discuss emerging therapeutic strategies targeting these pathways.
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