Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney

Sanjeev Kumar; Jing Liu; Paul Pang; A. Michaela Krautzberger; Antoine Reginensi; Haruhiko Akiyama; Andreas Schedl; Benjamin D. Humphreys; Andrew P. McMahon

doi:10.1016/j.celrep.2015.07.034

Cell Reports (Aug 2015)

Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney

Sanjeev Kumar,
Jing Liu,
Paul Pang,
A. Michaela Krautzberger,
Antoine Reginensi,
Haruhiko Akiyama,
Andreas Schedl,
Benjamin D. Humphreys,
Andrew P. McMahon

Affiliations

Sanjeev Kumar: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Jing Liu: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Paul Pang: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
A. Michaela Krautzberger: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Antoine Reginensi: INSERM U636, Universite de Nice-Sophia Anitpolis, Centre de Biochimie, Parc Valrose, 06108 Nice Cedex 02, France
Haruhiko Akiyama: Department of Orthopedics, Gifu University, Gifu 501-1194, Japan
Andreas Schedl: INSERM U636, Universite de Nice-Sophia Anitpolis, Centre de Biochimie, Parc Valrose, 06108 Nice Cedex 02, France
Benjamin D. Humphreys: Renal Division, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Andrew P. McMahon: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA

DOI: https://doi.org/10.1016/j.celrep.2015.07.034
Journal volume & issue: Vol. 12, no. 8
pp. 1325 – 1338

Abstract

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After acute kidney injury (AKI), surviving cells within the nephron proliferate and repair. We identify Sox9 as an acute epithelial stress response in renal regeneration. Translational profiling after AKI revealed a rapid upregulation of Sox9 within proximal tubule (PT) cells, the nephron cell type most vulnerable to AKI. Descendants of Sox9+ cells generate the bulk of the nephron during development and regenerate functional PT epithelium after AKI-induced reactivation of Sox9 after renal injury. After restoration of renal function post-AKI, persistent Sox9 expression highlights regions of unresolved damage within injured nephrons. Inactivation of Sox9 in PT cells pre-injury indicates that Sox9 is required for the normal course of post-AKI recovery. These findings link Sox9 to cell intrinsic mechanisms regulating development and repair of the mammalian nephron.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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