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Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice.

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Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. / Hartleben, Björn; Gödel, Markus; Meyer-Schwesinger, Catherine; Liu, Shuya; Ulrich, Theresa; Köbler, Sven; Wiech, Thorsten; Grahammer, Florian; Arnold, Sebastian J; Lindenmeyer, Maja T; Cohen, Clemens D; Pavenstädt, Hermann; Kerjaschki, Dontscho; Mizushima, Noboru; Shaw, Andrey S; Walz, Gerd; Huber, Tobias B.

in: J CLIN INVEST, Jahrgang 120, Nr. 4, 4, 2010, S. 1084-1096.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Hartleben, B, Gödel, M, Meyer-Schwesinger, C, Liu, S, Ulrich, T, Köbler, S, Wiech, T, Grahammer, F, Arnold, SJ, Lindenmeyer, MT, Cohen, CD, Pavenstädt, H, Kerjaschki, D, Mizushima, N, Shaw, AS, Walz, G & Huber, TB 2010, 'Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice.', J CLIN INVEST, Jg. 120, Nr. 4, 4, S. 1084-1096. <http://www.ncbi.nlm.nih.gov/pubmed/20200449?dopt=Citation>

APA

Hartleben, B., Gödel, M., Meyer-Schwesinger, C., Liu, S., Ulrich, T., Köbler, S., Wiech, T., Grahammer, F., Arnold, S. J., Lindenmeyer, M. T., Cohen, C. D., Pavenstädt, H., Kerjaschki, D., Mizushima, N., Shaw, A. S., Walz, G., & Huber, T. B. (2010). Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J CLIN INVEST, 120(4), 1084-1096. [4]. http://www.ncbi.nlm.nih.gov/pubmed/20200449?dopt=Citation

Vancouver

Hartleben B, Gödel M, Meyer-Schwesinger C, Liu S, Ulrich T, Köbler S et al. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J CLIN INVEST. 2010;120(4):1084-1096. 4.

Bibtex

@article{43658cbfb48a4713baa08cc178218415,
title = "Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice.",
abstract = "Injury and loss of podocytes are leading factors of glomerular disease and renal failure. The postmitotic podocyte is the primary glomerular target for toxic, immune, metabolic, and oxidant stress, but little is known about how this cell type copes with stress. Recently, autophagy has been identified as a major pathway that delivers damaged proteins and organelles to lysosomes in order to maintain cellular homeostasis. Here we report that podocytes exhibit an unusually high level of constitutive autophagy. Podocyte-specific deletion of autophagy-related 5 (Atg5) led to a glomerulopathy in aging mice that was accompanied by an accumulation of oxidized and ubiquitinated proteins, ER stress, and proteinuria. These changes resulted ultimately in podocyte loss and late-onset glomerulosclerosis. Analysis of pathophysiological conditions indicated that autophagy was substantially increased in glomeruli from mice with induced proteinuria and in glomeruli from patients with acquired proteinuric diseases. Further, mice lacking Atg5 in podocytes exhibited strongly increased susceptibility to models of glomerular disease. These findings highlight the importance of induced autophagy as a key homeostatic mechanism to maintain podocyte integrity. We postulate that constitutive and induced autophagy is a major protective mechanism against podocyte aging and glomerular injury, representing a putative target to ameliorate human glomerular disease and aging-related loss of renal function.",
author = "Bj{\"o}rn Hartleben and Markus G{\"o}del and Catherine Meyer-Schwesinger and Shuya Liu and Theresa Ulrich and Sven K{\"o}bler and Thorsten Wiech and Florian Grahammer and Arnold, {Sebastian J} and Lindenmeyer, {Maja T} and Cohen, {Clemens D} and Hermann Pavenst{\"a}dt and Dontscho Kerjaschki and Noboru Mizushima and Shaw, {Andrey S} and Gerd Walz and Huber, {Tobias B}",
year = "2010",
language = "Deutsch",
volume = "120",
pages = "1084--1096",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

RIS

TY - JOUR

T1 - Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice.

AU - Hartleben, Björn

AU - Gödel, Markus

AU - Meyer-Schwesinger, Catherine

AU - Liu, Shuya

AU - Ulrich, Theresa

AU - Köbler, Sven

AU - Wiech, Thorsten

AU - Grahammer, Florian

AU - Arnold, Sebastian J

AU - Lindenmeyer, Maja T

AU - Cohen, Clemens D

AU - Pavenstädt, Hermann

AU - Kerjaschki, Dontscho

AU - Mizushima, Noboru

AU - Shaw, Andrey S

AU - Walz, Gerd

AU - Huber, Tobias B

PY - 2010

Y1 - 2010

N2 - Injury and loss of podocytes are leading factors of glomerular disease and renal failure. The postmitotic podocyte is the primary glomerular target for toxic, immune, metabolic, and oxidant stress, but little is known about how this cell type copes with stress. Recently, autophagy has been identified as a major pathway that delivers damaged proteins and organelles to lysosomes in order to maintain cellular homeostasis. Here we report that podocytes exhibit an unusually high level of constitutive autophagy. Podocyte-specific deletion of autophagy-related 5 (Atg5) led to a glomerulopathy in aging mice that was accompanied by an accumulation of oxidized and ubiquitinated proteins, ER stress, and proteinuria. These changes resulted ultimately in podocyte loss and late-onset glomerulosclerosis. Analysis of pathophysiological conditions indicated that autophagy was substantially increased in glomeruli from mice with induced proteinuria and in glomeruli from patients with acquired proteinuric diseases. Further, mice lacking Atg5 in podocytes exhibited strongly increased susceptibility to models of glomerular disease. These findings highlight the importance of induced autophagy as a key homeostatic mechanism to maintain podocyte integrity. We postulate that constitutive and induced autophagy is a major protective mechanism against podocyte aging and glomerular injury, representing a putative target to ameliorate human glomerular disease and aging-related loss of renal function.

AB - Injury and loss of podocytes are leading factors of glomerular disease and renal failure. The postmitotic podocyte is the primary glomerular target for toxic, immune, metabolic, and oxidant stress, but little is known about how this cell type copes with stress. Recently, autophagy has been identified as a major pathway that delivers damaged proteins and organelles to lysosomes in order to maintain cellular homeostasis. Here we report that podocytes exhibit an unusually high level of constitutive autophagy. Podocyte-specific deletion of autophagy-related 5 (Atg5) led to a glomerulopathy in aging mice that was accompanied by an accumulation of oxidized and ubiquitinated proteins, ER stress, and proteinuria. These changes resulted ultimately in podocyte loss and late-onset glomerulosclerosis. Analysis of pathophysiological conditions indicated that autophagy was substantially increased in glomeruli from mice with induced proteinuria and in glomeruli from patients with acquired proteinuric diseases. Further, mice lacking Atg5 in podocytes exhibited strongly increased susceptibility to models of glomerular disease. These findings highlight the importance of induced autophagy as a key homeostatic mechanism to maintain podocyte integrity. We postulate that constitutive and induced autophagy is a major protective mechanism against podocyte aging and glomerular injury, representing a putative target to ameliorate human glomerular disease and aging-related loss of renal function.

M3 - SCORING: Zeitschriftenaufsatz

VL - 120

SP - 1084

EP - 1096

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 4

M1 - 4

ER -