Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel

Kaice A. LaFavers; Etienne Macedo; Pranav S. Garimella; Camila Lima; Shehnaz Khan; Jered Myslinski; Jeanette McClintick; Frank A. Witzmann; Seth Winfree; Carrie L. Phillips; Takashi Hato; Pierre C. Dagher; Xue-Ru Wu; Tarek M. El-Achkar; Radmila Micanovic

doi:10.1126/scitranslmed.aaw3639

Research ArticleKidney Disease

Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel

Kaice A. LaFavers¹,
Etienne Macedo²,
Pranav S. Garimella²,
Camila Lima³,
Shehnaz Khan¹,
Jered Myslinski¹,
Jeanette McClintick⁴,
Frank A. Witzmann⁵,
Seth Winfree¹,⁵,
Carrie L. Phillips⁶,
Takashi Hato¹,
Pierre C. Dagher¹,⁵,⁷,
Xue-Ru Wu⁸,
Tarek M. El-Achkar ¹,⁵,⁷,⁹,*,† and
Radmila Micanovic¹

¹Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
²Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA 92093, USA.
³Division of Nephrology, Department of Medicine, University of Sao Paulo, Sao Paulo 05403, Brazil.
⁴Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁵Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁶Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁷Richard L. Roudebush VA Medical Center, Indianapolis, IN 46202, USA.
⁸Departments of Urology and Pathology, New York University School of Medicine and Veterans Affairs, New York Harbor Healthcare System, Manhattan Campus, New York, NY 10010, USA.
⁹Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

↵†Corresponding author. Email: telachka{at}iu.edu

↵* Present address: Division of Nephrology, Indiana University School of Medicine, 950 W. Walnut, R2 202, Indianapolis, IN 46202, USA.

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Science Translational Medicine 02 Oct 2019:
Vol. 11, Issue 512, eaaw3639
DOI: 10.1126/scitranslmed.aaw3639

Kaice A. LaFavers

Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Etienne Macedo

Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA 92093, USA.

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Pranav S. Garimella

Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA 92093, USA.

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Camila Lima

Division of Nephrology, Department of Medicine, University of Sao Paulo, Sao Paulo 05403, Brazil.

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Shehnaz Khan

Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Jered Myslinski

Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Jeanette McClintick

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Frank A. Witzmann

Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Seth Winfree

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Carrie L. Phillips

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Takashi Hato

Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Pierre C. Dagher

Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.Richard L. Roudebush VA Medical Center, Indianapolis, IN 46202, USA.

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Xue-Ru Wu

Departments of Urology and Pathology, New York University School of Medicine and Veterans Affairs, New York Harbor Healthcare System, Manhattan Campus, New York, NY 10010, USA.

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Tarek M. El-Achkar

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For correspondence: telachka@iu.edu

Radmila Micanovic

Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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