Klotho: an antiaging protein involved in mineral and vitamin D metabolism.
Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders, including hypoactivity, sterility, skin thinning, muscle atrophy, osteoporosis, vascular calcifications, soft-tissue calcifications, defective hearing, thymus atrophy, pulmonary emphysema, ataxia, and abnormalities of the pituitary gland, as well as hypoglycemia, hyperphosphatemia, and paradoxically high-plasma calcitriol levels. Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered. Klotho can act as a circulating factor or hormone, which binds to a not yet identified high-affinity receptor and inhibits the intracellular insulin/insulin-like growth factor-1 (IGF-1) signaling cascade; klotho can function as a novel beta-glucuronidase, which deglycosylates steroid beta-glucuronides and the calcium channel transient receptor potential vallinoid-5 (TRPV5); as a cofactor essential for the stimulation of fibroblast growth factor (FGF) receptor by FGF23. The two last functions have propelled klotho to the group of key factors regulating mineral and vitamin D metabolism, and have also stimulated the interest of the nephrology community. The purpose of this review is to provide a nephrology-oriented overview of klotho and its potential implications in normal and altered renal function states.
Torres
P-Ureña
PU
Service de Néphrologie et Dialyse, Clinique de l'Orangerie, Aubervilliers, France. urena.pablo@wanadoo.fr
Prié
D
D
Molina-Blétry
V
V
Beck
L
L
Silve
C
C
Friedlander
G
G
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D000090265:Klotho Proteins; D008903:Minerals / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D008903:Minerals; D012333:RNA, Messenger; D014807:Vitamin D; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins