JCNRJournal of Clinical and Nursing Research2208-36852208-3693Bio-Byword Scientific Publishing Pty. Ltd.10.26689/jcnr.v9i8.11798ArticleThe Mechanism by Which AGE Activates EGFR-mediated Diabetic Kidney Disease Fibrosis by Regulating the Balance of Tyrosine Phosphatase SHP1/SHP2https://artdesignp.com/journal/JCNR/9/8/10.26689/jcnr.v9i8.11798LiLin,ZhangLimin,JiJuan,ZhangQian,LiSong,WangQian2025982025-09-04Objective: To investigate the mechanism by which advanced glycation end products (AGEs) promote diabetic kidney disease fibrosis by regulating the tyrosine phosphatase SHP1/SHP2 balance and activating the epidermal growth factor receptor (EGFR) pathway. Methods: Animal experiments and in vitro cell experiments were conducted using Western blot analysis and tissue cell staining to detect the expression of relevant proteins and cellular morphological changes. Results: AGEs disrupt the SHP1/SHP2 balance, activate the EGFR and TGFβ pathways, and promote fibrosis in diabetic nephropathy. Conclusion: AGEs regulate the balance of tyrosine phosphatases SHP1/SHP2, activate the EGFR-mediated signaling pathway, promote the release of inflammatory factors, and ultimately lead to fibrosis in diabetic nephropathy through a novel mechanism.

Zhao G, Liu J, Zeng H, et al., 2025, Research on Renal Fibrosis in Diabetic Nephropathy and Recent Advances in Treatment. Chinese Contemporary Medicine, 32(18): 176–179+183.

Du Y, Lei Y, Lin Y, et al., 2025, Research Progress on the Mechanism of Mesenchymal Stem Cells in Diabetic Nephropathy. Chinese Medical Innovation, 22(19): 180–185.

Ma X, Sun G, Yang Y, et al., 2025, Investigation of the Improvement of Cell Pyroptosis in Diabetic Nephropathy Mice by the Traditional Chinese Medicine Formula Yitang Kang via the TLR4/NF-κB/NLRP3 Signalling Pathway. Journal of Liaoning University of Traditional Chinese Medicine, 2025: 1–12.

Wang Y, Wang H, Yang L, et al., 2025, Fer-1 Inhibits Iron Death via the HSF-1/HO-1 Pathway to Alleviate Diabetic Kidney Disease Injury. Journal of Huazhong University of Science and Technology (Medical Edition), 54(03): 305–311.

Yang Y, Zhang C, 2025, Renal Protective Effects of Mineralocorticoid Receptor Antagonists in Patients with Diabetic Kidney Disease and Their Mechanisms. Shanghai Medicine, 46(06): 7–10+42.

Wen Y, Xiong W, Liu C, et al., 2025, Investigation of the Effects of DNJ, an Extract from Bombyx mori, on Renal Fibrosis and Glucose–Lipid Metabolism in Diabetic Mice via the AMPK/SIRT1–FoxO1 Pathway. Anhui Medicine, 29(06): 1114–1120+1274–1275.

Jin S, 2025, Effects of HDAC6 on Epithelial–Mesenchymal Transition in Diabetic Kidney Disease and Its Molecular Mechanisms, thesis, Ganzhou Medical University.

Liang L, Zhang Y, Shao S, et al., 2024, Application of Myeloid-Derived Suppressive Cell–Derived Exosomes for the Treatment of Diabetic Nephropathy in Mice. Modern Immunology, 44(06): 474–481.

Zhang Y, Gao B, Qian H, et al., 2025, GSTM3 Regulates Pyroptosis in Renal Tubular Epithelial Cells and Participates in the Renal Inflammatory Response Mechanism of Hyperuricemia. Modern Immunology, 45(04): 422–430.

Lu C, Shan X, Wang C, et al., 2025, Mechanism of Action of Gui Ren Ning in Inhibiting Mesangial Proliferation and Improving Renal Fibrosis in Diabetic Nephropathy. World Journal of Traditional Chinese Medicine, 20(10): 1699–1704+1712.

Jin R, Zhou F, Bao Y, et al., 2025, Research Progress on the Regulation of P53 by Traditional Chinese Medicine in the Treatment of Diabetic Nephropathy. Journal of Yunnan Traditional Chinese Medicine, 46(06): 86–94.

Yang Y, Zhang C, 2025, Research Progress on the Renal Protective Effects and Mechanisms of Mineralocorticoid Receptor Antagonists in Patients with Diabetic Nephropathy. Shanghai Medicine, 46(06): 7–10+42.