{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:04:16Z","timestamp":1792037056641,"version":"4.4.0"},"reference-count":29,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2005,11]]},"abstract":"<jats:p>The parathyroid hyperplasia secondary to kidney disease is associated with enhanced expression of the growth promoter transforming growth factor-\u03b1 (TGF-\u03b1). TGF-\u03b1 stimulates growth through activation of its receptor, the epidermal growth factor receptor (EGFR), normally expressed in the parathyroid glands. Because enhanced coexpression of TGF-\u03b1 and EGFR causes aggressive cellular growth, these studies utilized highly specific inhibitors of EGFR tyrosine kinase, a step mandatory for TGF-\u03b1-induced EGFR activation, to assess the contribution of growth signals from enhanced expression of TGF-\u03b1 exclusively or both TGF-\u03b1 and EGFR to the rapid parathyroid growth induced by kidney disease and exacerbated by high-phosphorus (P) and low-calcium (Ca) diets in rats. The enhancement in parathyroid gland weight and proliferating activity (proliferating cell nuclear antigen\/Ki67) induced by kidney disease and aggravated by either high P or low Ca intake, within the first week after 5\/6 nephrectomy, in rats, coincided with simultaneous increases (2- to 3-fold) in TGF-\u03b1 and EGFR content. Conversely, prevention of the increases in both TGF-\u03b1 and EGFR paralleled the efficacy of either P restriction or high-Ca intake in ameliorating uremia-induced parathyroid hyperplasia. More importantly, suppression of TGF-\u03b1\/EGFR signaling, through prophylactic administration of potent and highly selective inhibitors of ligand-induced EGFR activation, completely prevented both high-P- and low-Ca-induced parathyroid hyperplasia as well as TGF-\u03b1 self-upregulation. Thus enhanced parathyroid TGF-\u03b1\/EGFR expression, self-upregulation, and growth signals occur early in kidney disease, are aggravated by low-Ca and high-P intake, and constitute the main pathogenic mechanism of the severity of parathyroid hyperplasia.<\/jats:p>","DOI":"10.1152\/ajprenal.00167.2005","type":"journal-article","created":{"date-parts":[[2005,7,6]],"date-time":"2005-07-06T03:24:16Z","timestamp":1120620256000},"page":"F1096-F1102","source":"Crossref","is-referenced-by-count":60,"title":["A critical role for enhanced TGF-\u03b1 and EGFR expression in the initiation of parathyroid hyperplasia in experimental kidney 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