@article{16cc40af47d74939b4ae75d397c7f352,
title = "Renal Production, Uptake, and Handling of Circulating αklotho",
abstract = "αKlotho is amultifunctional protein highly expressed in the kidney. Soluble αKlotho is released through cleavage of the extracellular domain from membrane αKlotho by secretases to function as an endocrine/paracrine substance. The role of the kidney in circulating αKlotho production and handling is incompletely understood, however. Here, we found higher αKlotho concentration in suprarenal compared with infrarenal inferior vena cava in both rats and humans. In rats, serum αKlotho concentration dropped precipitously after bilateral nephrectomy or upon treatment with inhibitors of αKlotho extracellular domain shedding. Furthermore, the serum half-life of exogenous αKlotho in anephric rats was four- to five-fold longer than that in normal rats, and exogenously injected labeled recombinant αKlotho was detected in the kidney and in urine of rats. Both in vivo (micropuncture) and in vitro (proximal tubule cell line) studies showed that αKlotho traffics from the basal tothe apical side of the proximal tubule via transcytosis. Thus, we conclude that the kidney has dual roles in αKlotho homeostasis, producing and releasingaKlotho into the circulationandclearing αKlotho fromthebloodinto the urinary lumen.",
author = "Hu, {Ming C} and Mingjun Shi and Jianning Zhang and Addo, {Tayo A} and Cho, {Han Ju} and Barker, {Sarah L.} and Priya Ravikumar and Nancy Gillings and Ao Bian and Sidhu, {Sachdev S.} and Makoto Kuro-o and Moe, {Orson W}",
note = "Funding Information: This work was in part supported by the National Institutes of Health (R01-DK092461, R01-091392, and R01-DK13686), O''Brien Kidney Research Center at the University of Texas Southwestern Medical Center (P30-DK07938), American Heart Foundation Western Affiliate Beginning-Grant-in-Aid (0865235F), the Simmons Family Foundation, the Charles and Jane Pak Foundation, the Pak Center Innovative Research Support, and the Canadian Institutes of Health Research (MOP-93725). The authors would like to thank Dr. Philipp Scherer for assistance with infrared dye labeling and for providing infrared scan system, and Drs. Michel Baum, Jyothsna Gattineni and Xiao Yan for helpful discussions during the preparation of the manuscript. Authors are grateful to Ms. Jean Paek for technical support, and to Ms. Carolyn Griffith for assistance in enrollment of research subjects. A.B. was in part supported by Visiting Scholar Award from National Natural Science Foundation of China (81170660H0509, 81270408H0220), and Provincial Natural Science Foundation of Jiangsu, China (BK2011849). Publisher Copyright: {\textcopyright} 2016 by the American Society of Nephrology.",
year = "2016",
month = jan,
doi = "10.1681/ASN.2014101030",
language = "English (US)",
volume = "27",
pages = "79--90",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "1",
}