A novel therapeutic effect of statins on nephrogenic diabetes insipidus

Journal of Cellular and Molecular Medicine

Leonilde Bonfrate³  Giuseppe Procino²  David Q.-H. Wang¹  Maria Svelto² 

[1] Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA;Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Bari, Italy;Department of Biomedical Sciences and Human Oncology, Internal Medicine, University Medical School, Bari, Italy

关键词: apical membrane;    aquaporin;    cholesterol‐lowering drugs;    hypercholesterolaemia;    HMG‐CoA;    kidney;    nephrogenic diabetes insipidus;    vasopressin;    water channels;   

DOI  :  10.1111/jcmm.12422

来源: Wiley

【 摘 要 】

Abstract

Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase, resulting in reduced plasma total and low-density lipoprotein cholesterol levels. Recently, it has been shown that statins exert additional ‘pleiotropic’ effects by increasing expression levels of the membrane water channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a critical role in determining cellular water content. This additional effect is independent of cholesterol homoeostasis, and depends on depletion of mevalonate-derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2, statins increase water reabsorption by the kidney, thus opening up a new avenue in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary disease that yet lacks high-powered and limited side effects therapy. Aspects related to water balance determined by AQP2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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