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ADAM17, a New Player in the Pathogenesis of Chronic Kidney Disease-Mineral and Bone Disorder
- Source :
- Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 27(6)
- Publication Year :
- 2017
-
Abstract
- The triad composed by α-Klotho, fibroblast growth factor-23, and its receptor are involved in the pathogenesis of chronic kidney disease–mineral and bone disorder. A disintegrin and metalloproteinase 17 (ADAM17) is a metalloproteinase causing the proteolytic shedding of α-Klotho from the cell membrane, and its role in chronic kidney disease–mineral and bone disorder is not yet known. We studied the circulating levels of the above-mentioned mediators in patients with secondary hyperparathyroidism due to uremia, compared to control subjects, as well as in patients with primary hyperparathyroidism. We also measured the immunofluorescence pattern of the relevant tissue proteins in specimens obtained from patients undergoing parathyroid surgery for secondary compared to primary hyperparathyroidism. Results showed that α-Klotho tissue levels are reduced, in the presence of increased ADAM17 tissue levels. In addition, we showed increased serum levels of the main product of ADAM17 proteolytic activity, tumor necrosis factor-α. Thus, we found a paradoxical situation, in secondary compared to primary hyperparathyroidism, that is, that in the face of increased tumor necrosis factor-α in circulation, both soluble and tissue α-Klotho are reduced significantly, despite increased tissue ADAM17. In conclusion, tissue and serum levels of α-Klotho seem to have become independent from the regulation induced by ADAM17, which constitutes therefore another tassel in the impaired α-Klotho–FGF23 receptor axis present in uremia.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Settore MED/18 - CHIRURGIA GENERALE
030232 urology & nephrology
Medicine (miscellaneous)
ADAM17 Protein
urologic and male genital diseases
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Chronic kidney disease-mineral and bone disorder
Renal Dialysis
Internal medicine
Nutrition and Dietetic
Medicine
Humans
Klotho Proteins
Glucuronidase
Uremia
Chronic Kidney Disease-Mineral and Bone Disorder
Kidney
Metalloproteinase
Hyperparathyroidism
Nutrition and Dietetics
business.industry
Tumor Necrosis Factor-alpha
Hydrogen-Ion Concentration
medicine.disease
female genital diseases and pregnancy complications
Fibroblast Growth Factors
Fibroblast Growth Factor-23
030104 developmental biology
medicine.anatomical_structure
Endocrinology
C-Reactive Protein
Nephrology
Parathyroid Hormone
Case-Control Studies
Secondary hyperparathyroidism
Hyperparathyroidism, Secondary
business
Primary hyperparathyroidism
Subjects
Details
- ISSN :
- 15328503
- Volume :
- 27
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation
- Accession number :
- edsair.doi.dedup.....a514a9704dc1f71f5ff00fe22a2806a7