1,25-Dihydroxyvitamin D downregulation of TGFalpha/EGFR expression and growth signaling: a mechanism for the antiproliferative actions of the sterol in parathyroid hyperplasia of renal failure

The Journal of Steroid Biochemistry and Molecular Biology
Adriana S DussoE A Slatopolsky

Abstract

Elevated serum levels of parathyroid hormone (PTH) contribute to the increased morbidity and mortality in renal failure patients. Parathyroid gland hyperplasia is a major cause of high serum PTH. The present studies used the rat model of renal failure to address the mechanisms underlying uremia-induced parathyroid hyperplasia and the antiproliferative properties of vitamin D therapy (1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)) or its less calcemic analogs). Enhanced TGFalpha/EGFR co-expression is the major mitogenic signal in uremic parathyroid glands. At early stages of renal failure, vitamin D therapy efficiently counteracts uremia- and high phosphorus-induced hyperplasia by inhibiting the increases in parathyroid-TGFalpha/EGFR co-expression. In established hyperparathyroidism, characterized by highly enhanced-TGFalpha/EGFR co-expression, vitamin D therapy arrests growth by suppressing EGFR-growth signals from the plasma membrane and nuclear EGFR actions as a transactivator of the cyclin D1 gene, an important contributor to parathyroid hyperplasia in humans. In advanced renal failure, reduced-parathyroid vitamin D receptor levels limits the antiproliferative efficacy of vitamin D therapy. However, non-antiproliferative doses of...Continue Reading

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Citations

Mar 1, 2005·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Kenneth B Jonsson
Nov 1, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Gerald MillerCharles M Henley
Aug 4, 2005·Seminars in Dialysis·Dennis L Andress
Sep 23, 2009·The Journal of Clinical Investigation·Rajiv Kumar
Feb 22, 2011·Journal of the American Society of Nephrology : JASN·Qian ZhangJing Chen
Jul 1, 2006·Kidney International. Supplement·A S DussoE Slatopolsky
Jan 30, 2013·Molecular Carcinogenesis·Natalie NemazannikovaCrispin R Dass
Jul 19, 2013·International Journal of Cosmetic Science·K v q Lu'o'ng, L T H Nguyễn
Jul 25, 2009·American Journal of Physiology. Renal Physiology·José M ValdivielsoElvira Fernández
Sep 1, 2019·Reviews in Endocrine & Metabolic Disorders·Anna Maria FormentiAndrea Giustina
May 24, 2007·The International Journal of Artificial Organs·M Cozzolino, D Brancaccio
Apr 14, 2009·The International Journal of Artificial Organs·Mario CozzolinoDiego Brancaccio
Apr 14, 2009·The International Journal of Artificial Organs·Maurizio GallieniDiego Brancaccio
Feb 2, 2008·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Dennis L AndressStuart M Sprague
Jan 4, 2007·Advances in Chronic Kidney Disease·Stephen Z Fadem, Sharon M Moe
Jun 15, 2011·Molecular and Cellular Endocrinology·Frank BienaiméJean Claude Souberbielle

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