期刊
NEPHROLOGY DIALYSIS TRANSPLANTATION
卷 27, 期 -, 页码 iv6-iv10出版社
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfs426
关键词
ageing; Klotho; inflammation; NF-kappaB; phosphate
资金
- ISCII
- FEDER [CP04/00060, PS09/00447, 06/0046]
- Sociedad Espanola de Nefrologia
- ISCIII-RETIC [REDinREN/RD06/0016]
- Comunidad de Madrid [CIFRA/S-BIO0283/2006]
- Fundacion Conchita Rabago
- Programa Intensificacion Actividad Investigadora (ISCIII/Agencia Lain-Entralgo/CM)
- Genzyme
- [S2010/BMD-2378]
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 ageinginflammation 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- or TWEAK through the canonical activation of the inflammatory transcription factor nuclear factor kappa B (NFB) 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 NFB 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.
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