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Abstract: TH-PO549

Resveratrol Ameliorates High-Phosphate-Induced VOT and AMC in CKD Through Regulating Wnt/β-Catenin Signaling

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Huang, Xiaowen, Nanjing Medical University, Nanjing, China
  • He, Weichun, Nanjing Medical University, 2nd Affiliated Hospital, Nanjing, JIANGSU , China
Background

Vascular smooth muscle cells (VSMCs) to osteoblast-like cells transdifferentiation (VOT) induced by high-phosphate is a crucial step in the development of arterial medial calcification (AMC) in patients with chronic kidney disease (CKD). Our previous study demonstrated that Wnt/β-catenin signaling played an important role in promoting VOT and calcification in VSMCs induced by high-phosphate. Studies in cancer field have confirmed that resveratrol, a natural polyphenol, could regulate Wnt/β-catenin signaling. However, the potential effect of resveratrol on VOT and AMC through Wnt/β-catenin signaling remains to be elucidated.

Methods

An animal model of chronic renal failure with AMC was established by feeding rats a diet containing 0.75% adenine and 0.9% phosphorus. VOT and AMC in arterial ring was induced by placing isolated thoracic aortic rings from mice in culture medium containing 10 mM β-glycerophosphoric acid (β-GP). VOT and calcification of cultured VSMCs was also induced by 10 mM β-GP. The effect of resveratrol on VOT and/or calcification was observed in the in vivo, ex vivo and in vitro models mentioned above. The regulation of resveratrol on Wnt/β-catenin signaling in VSMCs was also examined.

Results

Resveratrol ameliorated AMC in chronic renal failure rats fed with high-phosphate diet and calcium deposition in arterial rings and VSMCs cultured in a high-phosphate environment. Resveratrol suppressed the induction of Runx2, osteocalcin and osteopontin and restored the expression of SM22α in arterial rings and VSMCs treated with high-phosphate. In vitro, resveratrol inhibited the upregulation of two forms of active β-catenin, dephosphorylated on Ser37/Thr41 and phosphorylated on Ser675 sites, and β-catenin nuclear translocation, stimulated by high-phosphate. Furthermore, porcupine and wntless was induced in VSMCs treated with high-phosphate in a time-dependent manner, which could be inhibited by resveratrol. Resveratrol also inhibited the phosphorylation of LRP6 induced by high-phosphate. However, it seemed that resveratrol couldn't inhibit the expression of Runx2 induced by Wnt3a.

Conclusion

The results presented in our study suggest that through targeting Wnt/β-catenin signaling, which in turn impeding VOT induced by high-phosphate, resveratrol possesses an effect on retarding AMC in CKD.

Funding

  • Government Support - Non-U.S.