Norcantharidin (NCTD) is a potential anti-renal interstitial fibrotic drug. However, the underlying molecular mechanism of how NCTD works remains unclear. In this study, using both in vivo and in vitro models, we report that the level of β-catenin is positively correlated to the degree of renal interstitial fibrosis (RIF). Protein phosphatase 2A (PP2A) binds to β-catenin and suppresses its phosphorylation, thereby increasing the total β-catenin expression. Additionally, NCTD dramatically elevates the level of phosphorylated β-catenin and decreases total β-catenin expression in a dose-dependent manner, consequently leading to the reduction of RIF. Mechanistically, PP2A-mediated suppression of β-catenin phosphorylation is an essential target for the anti-renal interstitial fibrotic effect of NCTD. Therefore, we report a potential theoretical basis for clinical application of NCTD in treating RIF.
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Renal interstitial fibrosis
Protein phosphatase 2A
Unilateral ureter obstruction
- HK-2 cells:
Human proximal tubular cells
Collagen type I
Chronic kidney disease
Transforming growth factor-beta1
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This study was supported by the Natural Science Foundation of China (Grant No. 81100486 and 81370792), the Hunan Provincial Science and Technology Program of China (Grant No. 2017SK2072), and the Changsha Science and Technology Program of China (Grant No. kq1901122).
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Xiao, Z., Wen, L., Zeng, D. et al. Protein Phosphatase 2A Inhibiting β-Catenin Phosphorylation Contributes Critically to the Anti-renal Interstitial Fibrotic Effect of Norcantharidin. Inflammation (2020). https://doi.org/10.1007/s10753-019-01173-0
- protein phosphatase 2A
- renal interstitial fibrosis