The induction of C/EBP beta contributes to vitamin D inhibition of ADAM17 expression and parathyroid hyperplasia in kidney disease

摘要

In secondary hyperparathyroidism (SHPT), enhanced parathyroid levels of transforming growth factor-alpha (TGF alpha) increase EGF receptor (EGFR) activation causing parathyroid hyperplasia, high parathyroid hormone (PTH) and also reductions in vitamin D receptor (VDR) that limit vitamin D suppression of SHPT. Since anti-EGFR therapy is not an option in human SHPT, we evaluated ADAM17 as a therapeutic target to suppress parathyroid hyperplasia because ADAM17 is required to release mature TGF alpha, the most potent EGFR-activating ligand.