Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney.
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.
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.
Sanjeev
S
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
J
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
P
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
AM
Krautzberger
INSERM U636, Universite de Nice-Sophia Anitpolis, Centre de Biochimie, Parc Valrose, 06108 Nice Cedex 02, France.
Antoine
A
Reginensi
Department of Orthopedics, Gifu University, Gifu 501-1194, Japan.
Haruhiko
H
Akiyama
INSERM U636, Universite de Nice-Sophia Anitpolis, Centre de Biochimie, Parc Valrose, 06108 Nice Cedex 02, France.
Andreas
A
Schedl
Renal Division, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Benjamin D
BD
Humphreys
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. Electronic address: amcmahon@med.usc.edu.
Andrew P
AP
McMahon
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D019070:Cell Lineage; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009399:Nephrons / Q000166:cytology / Q000378:metabolism; D062326:Re-Epithelialization; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse