TY - JOUR
T1 - Vitamin D inhibition of TACE and prevention of renal osteodystrophy and cardiovascular mortality
AU - Dusso, Adriana
AU - Arcidiacono, Maria Vittoria
AU - Yang, Jing
AU - Tokumoto, Masanori
N1 - Funding Information:
This work was supported by grants to AD from NIDDK DK062713 , CEDAR (Center for D-Activation Research) , and Abbott Pharmaceuticals .
PY - 2010/7
Y1 - 2010/7
N2 - 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/TGFα-driven secondary hyperparathyroidism, but, more significantly, renal TACE/TGFα-driven fibrotic and inflammatory lesions to the renal parenchyma, and TACE/TNFα-driven systemic inflammation, which is known to aggravate renal and cardiovascular lesions and enhance the risk of vascular calcification and cardiovascular mortality.
AB - 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/TGFα-driven secondary hyperparathyroidism, but, more significantly, renal TACE/TGFα-driven fibrotic and inflammatory lesions to the renal parenchyma, and TACE/TNFα-driven systemic inflammation, which is known to aggravate renal and cardiovascular lesions and enhance the risk of vascular calcification and cardiovascular mortality.
KW - ADAM17
KW - Kidney disease
KW - Renoprotection
KW - Secondary hyperparathyroidism
UR - http://www.scopus.com/inward/record.url?scp=77954759029&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2010.03.064
DO - 10.1016/j.jsbmb.2010.03.064
M3 - Article
C2 - 20359533
AN - SCOPUS:77954759029
VL - 121
SP - 193
EP - 198
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
IS - 1-2
ER -