Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):193-8. doi: 10.1016/j.jsbmb.2010.03.064. Epub 2010 Mar 30.

Vitamin D inhibition of TACE and prevention of renal osteodystrophy and cardiovascular mortality.

Author information

  • 1Renal Division, Washington University School of Medicine, St. Louis, MO 63110, USA. adusso@wustl.edu

Abstract

In the course of kidney disease, the progressive loss of renal capacity to maintain normal serum levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) is a main contributor to parathyroid hyperplasia and high serum PTH. High PTH causes mineral and skeletal abnormalities predisposing to ectopic calcifications and increased mortality. Intriguingly, replacement therapy with 1,25(OH)2D or its less calcemic analogs was recently shown to improve survival in kidney disease patients through renal and cardiovascular protective actions that are independent of PTH suppression. This work presents preliminary evidence that 1,25(OH)2D inhibition of TACE (Tumor necrosis factor Alpha Converting Enzyme) is a potential common mechanism underlying the efficacy of therapy with 1,25(OH)2D or its analogs to improve outcomes in chronic kidney disease. 1,25(OH)2D prevents/moderates not only the onset and progression of parathyroid TACE/TGFalpha-driven secondary hyperparathyroidism, but, more significantly, renal TACE/TGFalpha-driven fibrotic and inflammatory lesions to the renal parenchyma, and TACE/TNFalpha-driven systemic inflammation, which is known to aggravate renal and cardiovascular lesions and enhance the risk of vascular calcification and cardiovascular mortality.

Copyright (c) 2010 Elsevier Ltd. All rights reserved.

PMID:
20359533
[PubMed - indexed for MEDLINE]
PMCID:
PMC2906659
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk