Membrane-bound Klotho is not expressed endogenously in healthy or uraemic human vascular tissue
| Autor: | Mencke, R., Harms, G., Mirkovic, K., Struik, J., Ark, J. van, Loon, E. van, Verkaik, M., Borst, M.H. de, Zeebregts, C.J., Hoenderop, J.G., Vervloet, M.G., Hillebrands, J.L., NIGRAM Consortium |
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| Přispěvatelé: | Nephrology, ICaR - Circulation and metabolism, Groningen Kidney Center (GKC), Lifestyle Medicine (LM), Vascular Ageing Programme (VAP), Man, Biomaterials and Microbes (MBM), Groningen Institute for Organ Transplantation (GIOT) |
| Rok vydání: | 2015 |
| Předmět: |
Fibroblast growth factor 23
CHRONIC KIDNEY-DISEASE medicine.medical_specialty RENAL-FAILURE Physiology SMOOTH-MUSCLE-CELLS PROTEIN Biology urologic and male genital diseases Klotho Physiology (medical) medicine.artery Internal medicine Chronic kidney disease medicine CARDIOVASCULAR EVENTS Kidney Aorta TRANSCRIPTS ENCODING MEMBRANE medicine.disease Cardiovascular disease GENE CALCIFICATION female genital diseases and pregnancy complications Blot MICE medicine.anatomical_structure Endocrinology Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] Smooth muscle cells Immunohistochemistry Cardiology and Cardiovascular Medicine Kidney disease Calcification GROWTH-FACTOR 23 |
| Zdroj: | Cardiovascular Research, 108, 220-31 Cardiovascular Research, 108(2), 220-231. Oxford University Press Mencke, R, Harms, G, Mirkovic, K, Struik, J, van Ark, J, Van Loon, E, Verkaik, M, de Borst, M H, Zeebregts, C J, Hoenderop, J G, Vervloet, M G & Hillebrands, J L 2015, ' Membrane-bound Klotho is not expressed endogenously in healthy or uraemic human vascular tissue ', Cardiovascular Research, vol. 108, no. 2, pp. 220-231 . https://doi.org/10.1093/cvr/cvv187 Cardiovascular Research, 108(2), 220-231 Cardiovascular Research, 108, 2, pp. 220-31 |
| ISSN: | 0008-6363 |
| DOI: | 10.1093/cvr/cvv187 |
| Popis: | Contains fulltext : 152471.pdf (Publisher’s version ) (Closed access) AIMS: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD), a disease state that is strongly associated with loss of renal and systemic (alpha-)Klotho. Reversely, murine Klotho deficiency causes marked medial calcification. It is therefore thought that Klotho conveys a vasculoprotective effect. Klotho expression in the vessel wall, however, is disputed. METHODS AND RESULTS: We assessed Klotho expression in healthy human renal donor arteries (n = 9), CKD (renal graft recipient) arteries (n = 10), carotid endarterectomy specimens (n = 8), other elastic arteries (three groups of n = 3), and cultured human aortic smooth muscle cells (HASMCs) (three primary cell lines), using immunohistochemistry (IHC), immunofluorescence, quantitative reverse transcriptase-polymerase chain reaction, and western blotting (WB). We have extensively validated anti-Klotho antibody KM2076 by comparing staining patterns with other anti-Klotho antibodies (SC-22220, SC-22218, and AF1819), competition assays with recombinant Klotho, IHC on Klotho-deficient kl/kl mouse kidney, and WB with recombinant Klotho. Using KM2076, we could not detect full-length Klotho in vascular tissues or HASMCs. On the mRNA level, using primers against all four exon junctions, klotho expression could not be detected either. Fibroblast growth factor 23 (FGF23) injections in mice induced FGF23 signalling in kidneys but not in the aorta, indicating the absence of Klotho-dependent FGF23 signalling in the aorta. CONCLUSION: Using several independent and validated methods, we conclude that full-length, membrane-bound Klotho is not expressed in healthy or uraemic human vascular tissue. |
| Databáze: | OpenAIRE |
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