Parathyroid-specific epidermal growth factor-receptor inactivation prevents uremia-induced parathyroid hyperplasia in mice

Maria Vittoria Arcidiacono, Jing Yang, Elvira Fernandez, Adriana Dusso

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Background In chronic kidney disease (CKD), parathyroid hyperplasia contributes to high serum parathyroid hormone (PTH) and also to an impaired suppression of secondary hyperparathyroidism by calcium, vitamin D and fibroblast growth factor 23 (FGF23). In rats, systemic inhibition of epidermal growth factor receptor (EGFR) activation markedly attenuated uremia-induced parathyroid hyperplasia and vitamin D receptor (VDR) loss, hence restoring the response to vitamin D. Therefore, we propose that parathyroid-specific EGFR inactivation should prevent CKD-induced parathyroid hyperplasia. Methods A dominant-negative human EGFR mutant, which forms non-functional heterodimers with full-length endogenous EGFR, was successfully targeted to the parathyroid glands (PTGs) of FVB/N mice, using the 5' €2 regulatory sequence of the PTH promoter. The parathyroid phenotype and serum chemistries of wild-type (WT) and transgenic mice were examined after 14 weeks of either sham operation or 75% renal mass reduction (NX). Results Both genotypes had similar morphology and body weight, and NX-induction enhanced similarly serum blood urea nitrogen compared with sham-operated controls. However, despite similar serum calcium, phosphate and FGF23 levels in NX mice of both genotypes, parathyroid EGFR inactivation sufficed to completely prevent the marked increases in PTG enlargement, serum PTH and in parathyroid levels of transforming growth factor-, a powerful EGFR-activator, and the VDR reductions observed in WT mice. Conclusion In CKD, parathyroid EGFR activation is essential for parathyroid hyperplasia and VDR loss, rendering this transgenic mouse a unique tool to scrutinize the pathogenesis of parathyroid and multiple organ dysfunction of CKD progression unrelated to parathyroid hyperplasia.

Original languageEnglish
Pages (from-to)434-440
Number of pages7
JournalNephrology Dialysis Transplantation
Issue number3
StatePublished - Mar 1 2015


  • calcium
  • phosphate
  • secondary hyperparathyroidism
  • transforming growth factor alpha
  • vitamin D receptor


Dive into the research topics of 'Parathyroid-specific epidermal growth factor-receptor inactivation prevents uremia-induced parathyroid hyperplasia in mice'. Together they form a unique fingerprint.

Cite this