Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions
SCIENTIFIC REPORTS
Authors: Watanabe, Ryuichi; Fujita, Nobuyuki; Sato, Yuiko; Kobayashi, Tami; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Kuro-o, Makoto; Michigami, Toshimi; Fukumoto, Seiji; Tsuji, Takashi; Toyama, Yoshiaki; Nakamura, Masaya; Matsumoto, Morio; Miyamoto, Takeshi
Abstract
Control of phosphate metabolism is crucial to regulate aging in mammals. Klotho is a well-known anti-aging factor that regulates phosphate metabolism: mice mutant or deficient in Klotho exhibit phenotypes resembling human aging. Here we show that ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) is required for Klotho expression under phosphate overload conditions. Loss-of-function Enpp1(ttw/ttw) mice under phosphate overload conditions exhibited phenotypes resembling human aging and Klotho mutants, such as short life span, arteriosclerosis and osteoporosis, with elevated serum 1,25(OH)(2)D-3 levels. Enpp1(ttw/ttw) mice also exhibited significantly reduced renal Klotho expression under phosphate overload conditions, and aging phenotypes in these mice were rescued by Klotho overexpression, a low vitamin D diet or vitamin D receptor knockout. These findings indicate that Enpp1 plays a crucial role in regulating aging via Klotho expression under phosphate overload conditions.
ENPP1 is a novel cell surface marker of germinal center and memory B cells and is highly expressed in plasma cells
JOURNAL OF IMMUNOLOGY
Authors: Wang, Hongsheng; Shin, Dong-Mi; Gonzalez-Garcia, Ines; Abbasi, Sadia; Feng, Jianxun; Morse, Herbert
Abstract