GDF11 improves tubular regeneration after acute kidney injury in elderly mice

被引:46
作者
Zhang, Ying [1 ,2 ]
Li, Qinggang [1 ]
Liu, Dong [1 ,3 ]
Huang, Qi [1 ]
Cai, Guangyan [1 ]
Cui, Shaoyuan [1 ]
Sun, Xuefeng [1 ]
Chen, Xiangmei [1 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Natl Clin Res Ctr Kidney Dis, Chinese PLA Inst Nephrol, Dept Nephrol,State Key Lab Kidney Dis, Beijing 100853, Peoples R China
[2] Nankai Univ, Med Coll, Tianjin 300071, Peoples R China
[3] Chinese PLA Air Force Gen Hosp, Dept Nephrol, Beijing 100142, Peoples R China
基金
中国国家自然科学基金;
关键词
DIFFERENTIATION FACTOR 11; EPITHELIAL-CELLS REPAIR; AGE; RECOVERY; MUSCLE; PROGRESSION; ACTIVATION; MYOSTATIN; SURVIVAL; RECEPTOR;
D O I
10.1038/srep34624
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia-reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2'-deoxyuridine (EdU)-positive proximal tubular epithelial cells. GDF11 improved the renal repair, recovery of renal function, and survival of elderly mice at 72 h after IRI. Moreover, the addition of recombinant GDF11 to primary renal epithelial cells increased proliferation, migration, and dedifferentiation by upregulating the ERK1/2 pathway in vitro. Our study indicates that GDF11/8 in the kidney decreases with age and that GDF11 can increase tubular cell dedifferentiation and proliferation as well as improve tubular regeneration after acute kidney injury (AKI) in old mice.
引用
收藏
页数:15
相关论文
共 38 条
[1]  
Ahn ST, 2016, CAN J VET RES, V80, P90
[2]   STAT3 attenuates EGFR-mediated ERK activation and cell survival during oxidant stress in mouse proximal tubular cells [J].
Arany, I. ;
Megyesi, J. K. ;
Nelkin, B. D. ;
Safirstein, R. L. .
KIDNEY INTERNATIONAL, 2006, 70 (04) :669-674
[3]   Origin of regenerating tubular cells after acute kidney injury [J].
Berger, Katja ;
Bangen, Joerg-Martin ;
Hammerich, Linda ;
Liedtke, Christian ;
Floege, Juergen ;
Smeets, Bart ;
Moeller, Marcus Johannes .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (04) :1533-1538
[4]   Deletion of the epidermal growth factor receptor in renal proximal tubule epithelial cells delays recovery from acute kidney injury [J].
Chen, Jianchun ;
Chen, Jian-Kang ;
Harris, Raymond C. .
KIDNEY INTERNATIONAL, 2012, 82 (01) :45-52
[5]   Kidney regeneration: common themes from the embryo to the adult [J].
Cirio, M. Cecilia ;
de Groh, Eric D. ;
de Caestecker, Mark P. ;
Davidson, Alan J. ;
Hukriede, Neil A. .
PEDIATRIC NEPHROLOGY, 2014, 29 (04) :553-564
[6]   An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia [J].
Dussiot, Michael ;
Maciel, Thiago T. ;
Fricot, Aurelie ;
Chartier, Celine ;
Negre, Olivier ;
Veiga, Joel ;
Grapton, Damien ;
Paubelle, Etienne ;
Payen, Emmanuel ;
Beuzard, Yves ;
Leboulch, Philippe ;
Ribeil, Jean-Antoine ;
Arlet, Jean-Benoit ;
Cote, Francine ;
Courtois, Genevieve ;
Ginzburg, Yelena Z. ;
Daniel, Thomas O. ;
Chopra, Rajesh ;
Sung, Victoria ;
Hermine, Olivier ;
Moura, Ivan C. .
NATURE MEDICINE, 2014, 20 (04) :398-+
[7]   GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration [J].
Egerman, Marc A. ;
Cadena, Samuel M. ;
Gilbert, Jason A. ;
Meyer, Angelika ;
Nelson, Hallie N. ;
Swalley, Susanne E. ;
Mallozzi, Carolyn ;
Jacobi, Carsten ;
Jennings, Lori L. ;
Clay, Ieuan ;
Laurent, Gaelle ;
Ma, Shenglin ;
Brachat, Sophie ;
Lach-Trifilieff, Estelle ;
Shavlakadze, Tea ;
Trendelenburg, Anne-Ulrike ;
Brack, Andrew S. ;
Glass, David J. .
CELL METABOLISM, 2015, 22 (01) :164-174
[8]   Regulation of metanephric kidney development by growth/differentiation factor 11 [J].
Esquela, AF ;
Lee, SJ .
DEVELOPMENTAL BIOLOGY, 2003, 257 (02) :356-370
[9]   In vivo functions of the proprotein convertase PC5/6 during mouse development:: Gdf11 is a likely substrate [J].
Essalmani, Rachid ;
Zaid, Ahmed ;
Marcinkiewicz, Jadwiga ;
Chamberland, Ann ;
Pasquato, Antonella ;
Seidah, Nabil G. ;
Prat, Annik .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (15) :5750-5755
[10]   Conditional Knockout of Proximal Tubule Mitofusin 2 Accelerates Recovery and Improves Survival after Renal Ischemia [J].
Gall, Jonathan M. ;
Wang, Zhiyong ;
Bonegio, Ramon G. ;
Havasi, Andrea ;
Liesa, Marc ;
Vemula, Pradheep ;
Borkan, Steven C. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2015, 26 (05) :1092-1102