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...
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doaj-be8ba7b556c640b4a085171c25aaf6bf2020-11-24T21:47:27ZengElsevierCell Reports2211-12472015-08-011281325133810.1016/j.celrep.2015.07.034Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian KidneySanjeev Kumar0Jing Liu1Paul Pang2A. Michaela Krautzberger3Antoine Reginensi4Haruhiko Akiyama5Andreas Schedl6Benjamin D. Humphreys7Andrew P. McMahon8Department 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, USADepartment 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, USADepartment 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, USADepartment 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, USAINSERM U636, Universite de Nice-Sophia Anitpolis, Centre de Biochimie, Parc Valrose, 06108 Nice Cedex 02, FranceDepartment of Orthopedics, Gifu University, Gifu 501-1194, JapanINSERM U636, Universite de Nice-Sophia Anitpolis, Centre de Biochimie, Parc Valrose, 06108 Nice Cedex 02, FranceRenal Division, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USADepartment 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, USAAfter 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.http://www.sciencedirect.com/science/article/pii/S2211124715007949 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sanjeev Kumar Jing Liu Paul Pang A. Michaela Krautzberger Antoine Reginensi Haruhiko Akiyama Andreas Schedl Benjamin D. Humphreys Andrew P. McMahon |
spellingShingle |
Sanjeev Kumar Jing Liu Paul Pang A. Michaela Krautzberger Antoine Reginensi Haruhiko Akiyama Andreas Schedl Benjamin D. Humphreys Andrew P. McMahon Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney Cell Reports |
author_facet |
Sanjeev Kumar Jing Liu Paul Pang A. Michaela Krautzberger Antoine Reginensi Haruhiko Akiyama Andreas Schedl Benjamin D. Humphreys Andrew P. McMahon |
author_sort |
Sanjeev Kumar |
title |
Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney |
title_short |
Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney |
title_full |
Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney |
title_fullStr |
Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney |
title_full_unstemmed |
Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney |
title_sort |
sox9 activation highlights a cellular pathway of renal repair in the acutely injured mammalian kidney |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2015-08-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124715007949 |
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