title: Overexpression of klotho protein modulates uninephrectomy-induced compensatory renal hypertrophy by suppressing IGF-I signals.
abstract: The klotho gene is highly expressed in the distal convoluted tubule of the kidney, while its encoded protein has many physiological and pathophysiological renal roles. We investigated the effect of klotho protein on physiological compensatory renal hypertrophy after nephrectomy in klotho transgenic (KLTG) mice. Renal hypertrophy was suppressed in KLTG mice compared with wild-type mice, and this was associated with suppression of insulin growth factor-1 (IGF-1) signaling by klotho protein. In vitro, IGF-1 signaling was suppressed in human proximal tubular cells transfected with the klotho plasmid. Our data suggest that klotho modulates compensatory renal hypertrophy after nephrectomy via suppression of the IGF-1 signaling pathway, indicating a novel physiological role for klotho protein in the kidney.
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan. zajiten1@gmail.com
authors.forename: Hajime
authors.initials: H
authors.lastname: Nagasu
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kuwabara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yorimitsu
authors.forename: Kengo
authors.initials: K
authors.lastname: Kidokoro
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishi
authors.forename: Naruya
authors.initials: N
authors.lastname: Tomita
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Kashihara
mesh_terms: D000818:Animals; D002460:Cell Line; D005966:Glucuronidase / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006984:Hypertrophy / Q000235:genetics / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D000090265:Klotho Proteins; D051379:Mice; D008822:Mice, Transgenic; D019255:NADPH Oxidases / Q000378:metabolism; D009392:Nephrectomy; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D019255:NADPH Oxidases; D058570:TOR Serine-Threonine Kinases; D005966:Glucuronidase; D000090265:Klotho Proteins