Basic ResearchInduction of Retinol Dehydrogenase 9 Expression in Podocytes Attenuates Kidney InjuryLi, Xuezhu*,†; Dai, Yan*,‡; Chuang, Peter Y.*; He, John Cijiang*,‡ Author Information *Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; †Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; and ‡Renal Section, James J. Peters Veterans Affairs Medical Center, Bronx, New York Correspondence: Dr. John Cijiang He, Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1243, New York, NY 10029. Email: [email protected] X.L. and Y.D. contributed equally to this work. The current affiliation for Y.D. is Division of Nephrology, Shanghai Medical College, Fudan University, Zhongshan Hospital, Shanghai, China. Received November 3, 2013 Accepted December 22, 2013 Journal of the American Society of Nephrology 25(9):p 1933-1941, September 2014. | DOI: 10.1681/ASN.2013111150 Buy Metrics Abstract The intracellular concentration of retinoic acid is determined by two sequential oxidation reactions that convert retinol to retinoic acid. We recently demonstrated that retinoic acid synthesis is significantly impaired in glomeruli of HIV-1 transgenic mice (Tg26), a murine model of HIV-associated nephropathy. This impaired retinoic acid synthesis correlates with reduced renal expression of retinol dehydrogenase 9, which catalyzes the rate-limiting step of retinoic acid synthesis by converting retinol to retinal. Because retinoic acid has renal protective effects and can induce podocyte differentiation, we hypothesized that restoration of retinoic acid synthesis could slow the progression of renal disease. Herein, we demonstrate that overexpression of retinol dehydrogenase 9 in cultured podocytes induces the expression of podocyte differentiation markers. Furthermore, we confirm that podocyte-specific overexpression of retinol dehydrogenase 9 in mice with established kidney disease due to either HIV-associated nephropathy or adriamycin-induced nephropathy decreases proteinuria, attenuates kidney injury, and restores podocyte differentiation markers. Our data suggest that restoration of retinoic acid synthesis could be a new approach to treat kidney disease. Copyright © 2014 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.