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AKT2 is essential to maintain podocyte viability and function during chronic kidney disease

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AKT2 is essential to maintain podocyte viability and function during chronic kidney disease. / Canaud, Guillaume; Bienaimé, Frank; Viau, Amandine; Treins, Caroline; Baron, William; Nguyen, Clément; Burtin, Martine; Berissi, Sophie; Giannakakis, Konstantinos; Muda, Andrea Onetti; Zschiedrich, Stefan; Huber, Tobias B; Friedlander, Gérard; Legendre, Christophe; Pontoglio, Marco; Pende, Mario; Terzi, Fabiola.

in: NAT MED, Jahrgang 19, Nr. 10, 10.2013, S. 1288-96.

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

Harvard

Canaud, G, Bienaimé, F, Viau, A, Treins, C, Baron, W, Nguyen, C, Burtin, M, Berissi, S, Giannakakis, K, Muda, AO, Zschiedrich, S, Huber, TB, Friedlander, G, Legendre, C, Pontoglio, M, Pende, M & Terzi, F 2013, 'AKT2 is essential to maintain podocyte viability and function during chronic kidney disease', NAT MED, Jg. 19, Nr. 10, S. 1288-96. https://doi.org/10.1038/nm.3313

APA

Canaud, G., Bienaimé, F., Viau, A., Treins, C., Baron, W., Nguyen, C., Burtin, M., Berissi, S., Giannakakis, K., Muda, A. O., Zschiedrich, S., Huber, T. B., Friedlander, G., Legendre, C., Pontoglio, M., Pende, M., & Terzi, F. (2013). AKT2 is essential to maintain podocyte viability and function during chronic kidney disease. NAT MED, 19(10), 1288-96. https://doi.org/10.1038/nm.3313

Vancouver

Canaud G, Bienaimé F, Viau A, Treins C, Baron W, Nguyen C et al. AKT2 is essential to maintain podocyte viability and function during chronic kidney disease. NAT MED. 2013 Okt;19(10):1288-96. https://doi.org/10.1038/nm.3313

Bibtex

@article{df262305dd6444db9190fd1db83e4547,
title = "AKT2 is essential to maintain podocyte viability and function during chronic kidney disease",
abstract = "In chronic kidney disease (CKD), loss of functional nephrons results in metabolic and mechanical stress in the remaining ones, resulting in further nephron loss. Here we show that Akt2 activation has an essential role in podocyte protection after nephron reduction. Glomerulosclerosis and albuminuria were substantially worsened in Akt2(-/-) but not in Akt1(-/-) mice as compared to wild-type mice. Specific deletion of Akt2 or its regulator Rictor in podocytes revealed that Akt2 has an intrinsic function in podocytes. Mechanistically, Akt2 triggers a compensatory program that involves mouse double minute 2 homolog (Mdm2), glycogen synthase kinase 3 (Gsk3) and Rac1. The defective activation of this pathway after nephron reduction leads to apoptosis and foot process effacement of the podocytes. We further show that AKT2 activation by mammalian target of rapamycin complex 2 (mTORC2) is also required for podocyte survival in human CKD. More notably, we elucidate the events underlying the adverse renal effect of sirolimus and provide a criterion for the rational use of this drug. Thus, our results disclose a new function of Akt2 and identify a potential therapeutic target for preserving glomerular function in CKD.",
keywords = "Animals, Disease Progression, Humans, Kidney Failure, Chronic, Mice, Mice, Knockout, Multiprotein Complexes, Nephrons, Podocytes, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, Journal Article, Research Support, Non-U.S. Gov't",
author = "Guillaume Canaud and Frank Bienaim{\'e} and Amandine Viau and Caroline Treins and William Baron and Cl{\'e}ment Nguyen and Martine Burtin and Sophie Berissi and Konstantinos Giannakakis and Muda, {Andrea Onetti} and Stefan Zschiedrich and Huber, {Tobias B} and G{\'e}rard Friedlander and Christophe Legendre and Marco Pontoglio and Mario Pende and Fabiola Terzi",
year = "2013",
month = oct,
doi = "10.1038/nm.3313",
language = "English",
volume = "19",
pages = "1288--96",
journal = "NAT MED",
issn = "1078-8956",
publisher = "NATURE PUBLISHING GROUP",
number = "10",

}

RIS

TY - JOUR

T1 - AKT2 is essential to maintain podocyte viability and function during chronic kidney disease

AU - Canaud, Guillaume

AU - Bienaimé, Frank

AU - Viau, Amandine

AU - Treins, Caroline

AU - Baron, William

AU - Nguyen, Clément

AU - Burtin, Martine

AU - Berissi, Sophie

AU - Giannakakis, Konstantinos

AU - Muda, Andrea Onetti

AU - Zschiedrich, Stefan

AU - Huber, Tobias B

AU - Friedlander, Gérard

AU - Legendre, Christophe

AU - Pontoglio, Marco

AU - Pende, Mario

AU - Terzi, Fabiola

PY - 2013/10

Y1 - 2013/10

N2 - In chronic kidney disease (CKD), loss of functional nephrons results in metabolic and mechanical stress in the remaining ones, resulting in further nephron loss. Here we show that Akt2 activation has an essential role in podocyte protection after nephron reduction. Glomerulosclerosis and albuminuria were substantially worsened in Akt2(-/-) but not in Akt1(-/-) mice as compared to wild-type mice. Specific deletion of Akt2 or its regulator Rictor in podocytes revealed that Akt2 has an intrinsic function in podocytes. Mechanistically, Akt2 triggers a compensatory program that involves mouse double minute 2 homolog (Mdm2), glycogen synthase kinase 3 (Gsk3) and Rac1. The defective activation of this pathway after nephron reduction leads to apoptosis and foot process effacement of the podocytes. We further show that AKT2 activation by mammalian target of rapamycin complex 2 (mTORC2) is also required for podocyte survival in human CKD. More notably, we elucidate the events underlying the adverse renal effect of sirolimus and provide a criterion for the rational use of this drug. Thus, our results disclose a new function of Akt2 and identify a potential therapeutic target for preserving glomerular function in CKD.

AB - In chronic kidney disease (CKD), loss of functional nephrons results in metabolic and mechanical stress in the remaining ones, resulting in further nephron loss. Here we show that Akt2 activation has an essential role in podocyte protection after nephron reduction. Glomerulosclerosis and albuminuria were substantially worsened in Akt2(-/-) but not in Akt1(-/-) mice as compared to wild-type mice. Specific deletion of Akt2 or its regulator Rictor in podocytes revealed that Akt2 has an intrinsic function in podocytes. Mechanistically, Akt2 triggers a compensatory program that involves mouse double minute 2 homolog (Mdm2), glycogen synthase kinase 3 (Gsk3) and Rac1. The defective activation of this pathway after nephron reduction leads to apoptosis and foot process effacement of the podocytes. We further show that AKT2 activation by mammalian target of rapamycin complex 2 (mTORC2) is also required for podocyte survival in human CKD. More notably, we elucidate the events underlying the adverse renal effect of sirolimus and provide a criterion for the rational use of this drug. Thus, our results disclose a new function of Akt2 and identify a potential therapeutic target for preserving glomerular function in CKD.

KW - Animals

KW - Disease Progression

KW - Humans

KW - Kidney Failure, Chronic

KW - Mice

KW - Mice, Knockout

KW - Multiprotein Complexes

KW - Nephrons

KW - Podocytes

KW - Proto-Oncogene Proteins c-akt

KW - TOR Serine-Threonine Kinases

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/nm.3313

DO - 10.1038/nm.3313

M3 - SCORING: Journal article

C2 - 24056770

VL - 19

SP - 1288

EP - 1296

JO - NAT MED

JF - NAT MED

SN - 1078-8956

IS - 10

ER -