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- Title
Klotho, phosphate and inflammation/ageing in chronic kidney disease.
- Authors
Izquierdo, María C.; Perez-Gomez, María V.; Sanchez-Niño, María D.; Sanz, Ana B.; Ruiz-Andres, Olga; Poveda, Jonay; Moreno, Juan Antonio; Egido, Jesús; Ortiz, Alberto
- Abstract
Evidence is emerging for the inflammatory nature of many ageing-associated diseases, including atherosclerosis, vascular calcification, diabetes and chronic kidney disease (CKD), among others. Ageing itself results in chronic low-grade inflammation that promotes end-organ damage. Inflammatory organ damage, in turn, may contribute to inflammation. Recent research has identified the kidney-secreted hormone Klotho as a central player at the ageing–inflammation interface. Thus, systemic or local renal inflammation decreases kidney Klotho expression. Klotho down-regulation may be induced by specific cytokines such as tumour necrosis factor-α or TWEAK through the canonical activation of the inflammatory transcription factor nuclear factor kappa B (NFκB) and, specifically RelA. In addition, inflammatory cytokines lead to the epigenetic inactivation of Klotho transcription. Klotho itself has antioxidant and anti-inflammatory properties and the canonical NFκB component RelA is one of its targets. Klotho is a key regulator of phosphate balance and a role of phosphate in ageing has been shown. However, the potential relationship between phosphate and inflammation requires further clarification. A correct understanding of these interactions may lead to the design of novel therapeutic approaches to CKD and CKD-related inflammatory and ageing features as well as to inflammation/ageing in general.
- Subjects
KIDNEY disease treatments; INFLAMMATION; CLOTHO (Greek deity); PHOSPHATES; GENE expression; ANTI-inflammatory agents; ANTIOXIDANTS; AGE factors in disease
- Publication
Nephrology Dialysis Transplantation, 2012, Vol 27, Issue suppl_4, piv6
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfs426