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Abstract: FR-PO510

Accumulation of Activated β-Catenin in Uremic Hyperparathyroid Glands

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Wen, Ping, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
  • Hou, Dawei, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
  • Cao, Jinlong, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
  • Yang, Junwei, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
Background

Parathyroid proliferation may become nodular mainly in cases of advanced uremic hyperparathyroidism. The ubiquitously expressed multifunctional protein β-catenin displays important functions in the canonical Wnt signaling pathway by regulating cell proliferation and differentiation. Activation of Wnt/β-catenin pathway leads to stimulate aerobic glycolysis, called Warburg effect, which is validated the dominant metabolic style in tumor tissue. While hyperplasic parathyroid glands display similar pathology characteristics of tumor, the aim of this study is to evaluate whether the Wnt/β-catenin signaling pathway is activated in hyperplastic glands from sHPT patients and if Warburg effect is activated by β-catenin pathway.

Methods

Serum iPTH levels were measured by radio-immunity method. Hyperplastic parathyroid glands from sHPT patients (n=36) were acquired from patients during the operation. Normal parathyroid tissue (n=3) was obtained from glands inadvertently removed in conjunction with thyroid surgery. Real time RT-PCR and immunohistochemistry were performed to detect PCNA and activated β-catenin, and glycolytic enzymes.

Results

1. The average serum iPTH level was 1264.59±576.29 pg/ml of sHPT patients and 42.0±20.95 pg/ml of normal controls respectively. 2. HE staining revealed 5 diffuse hyperplasic glands and 31 nodular hyperplasic glands. 3. The mRNA and protein expression of PCNA was dramatically up-regulated compared to normal controls. 4. The expressions of activated β-catenin were increased in hyperplastic glands compared to normal glands. There was no difference between diffuse hyperplasic and nodular hyperplasic glands. Semiquantitative analysis didn’t reveal association between β-catenin and iPTH level. 5. The expressions of glycolytic enzymes: HK2, PFK and LDH were not up-regulated in hyperplasic glands compared to the normal glands. Semiquantitative analysis didn’t reveal associations between expressions of glycolytic enzymes and iPTH level.

Conclusion

Our results strongly suggest that modifications in the Wnt/β-catenin signaling pathway may be involved in the development of sHPT. However, aerobic glycolysis was not activated by β-catenin in hyperplasic glands. The precise mechanism is needed to be explored.

Funding

  • Government Support - Non-U.S.