Abstract
Background
Diabetic nephropathy (DN) is a common complication of diabetes. The Notch pathway plays an important role in podocyte injury and decreases the expression of podocyte-specific proteins in DN. However, the exact mechanisms are still elusive.
Objective
The purpose of this study was to investigate the effect of the Notch pathway on podocyte injury by regulating Krüppel-like factor 4 (KLF4) in high glucose (HG)-induced podocytes.
Methods
The expression of the Notch pathway and KLF4 was regulated in HG-induced podocytes. Western blotting was used to detect the protein expression of Notch1, Notch intracellular domain 1 (NICD1), KLF4, nephrin, and integrin β1. The mRNA levels of Notch1, KLF4, nephrin, and integrin β1 were determined by real-time polymerase chain reaction.
Results
HG increased the expression of Notch1 and NICD1 in podocytes and inhibited the expression of KLF4 (p < 0.05 or p < 0.01). Inhibition of the Notch pathway by DAPT increased the KLF4, nephrin, and integrin β1 levels in HG-induced podocytes (p < 0.01). Downregulation of KLF4 expression by KLF4-siRNA inhibited the expression of nephrin and integrin β1 in HG-induced podocytes (p < 0.01).
Conclusion
The Notch pathway may regulate the expression of nephrin and integrin β1 through KLF4 in HG-induced podocytes.
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Acknowledgements
This study was supported by the grants from the Hebei Natural Science Foundation of China (H2019206045).
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Yao, M., Wang, X., **u, X. et al. The Notch pathway regulates KLF4 in podocyte injury induced by high glucose. Int J Diabetes Dev Ctries 42, 489–494 (2022). https://doi.org/10.1007/s13410-021-00988-8
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DOI: https://doi.org/10.1007/s13410-021-00988-8