Tissue expression and source of circulating αKlotho.
αKlotho (Klotho), a type I transmembrane protein and a coreceptor for Fibroblast Growth Factor-23, was initially thought to be expressed only in a limited number of tissues, most importantly the kidney, parathyroid gland and choroid plexus. Emerging data may suggest a more ubiquitous Klotho expression pattern which has prompted reevaluation of the restricted Klotho paradigm. Herein we systematically review the evidence for Klotho expression in various tissues and cell types in humans and other mammals, and discuss potential reasons behind existing conflicting data. Based on current literature and tissue expression atlases, we propose a classification of tissues into high, intermediate and low/absent Klotho expression. The functional relevance of Klotho in organs with low expression levels remain uncertain and there is currently limited data on a role for membrane-bound Klotho outside the kidney. Finally, we review the evidence for the tissue source of soluble Klotho, and conclude that the kidney is likely to be the principal source of circulating Klotho in physiology.
Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. Electronic address: hannes.olauson@ki.se.
Hannes
H
Olauson
Division of Pathology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Rik
R
Mencke
Division of Pathology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Jan-Luuk
JL
Hillebrands
Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Tobias E
TE
Larsson
D000818:Animals; D002831:Choroid Plexus / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D010280:Parathyroid Glands / Q000378:metabolism
C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
FGF-23; FGF23; Klotho