TY - JOUR
T1 - Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney
AU - Kumar, Sanjeev
AU - Liu, Jing
AU - Pang, Paul
AU - Krautzberger, A. Michaela
AU - Reginensi, Antoine
AU - Akiyama, Haruhiko
AU - Schedl, Andreas
AU - Humphreys, Benjamin D.
AU - McMahon, Andrew P.
N1 - Funding Information:
We are grateful to Dr. Anton Valouev for advice on statistical analysis. S.K. was supported by John McKay Fellowship Award from University Kidney Research Organisation, Los Angeles. A.S. was supported by grants from the Agence Nationale de la Recherche (09-Geno-027-01; ANR-11-LABX-0028-01) and the Fondation Recherche Medicale. A.R. was supported by a fellowship from the Fondation Recherche Medicale. Work in A.P.M.’s laboratory was supported by a grant from the California Institute for Regenerative Medicine (LA1-06536).
Publisher Copyright:
© 2015 The Authors.
PY - 2015/8/25
Y1 - 2015/8/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84939796759&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.07.034
DO - 10.1016/j.celrep.2015.07.034
M3 - Article
C2 - 26279573
AN - SCOPUS:84939796759
SN - 2211-1247
VL - 12
SP - 1325
EP - 1338
JO - Cell Reports
JF - Cell Reports
IS - 8
M1 - 1940
ER -