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Role of mTOR in podocyte function and diabetic nephropathy in humans and mice

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Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. / Gödel, Markus; Hartleben, Björn; Herbach, Nadja; Liu, Shuya; Zschiedrich, Stefan; Lu, Shun; Debreczeni-Mór, Andrea; Lindenmeyer, Maja T; Rastaldi, Maria-Pia; Hartleben, Götz; Wiech, Thorsten; Fornoni, Alessia; Nelson, Robert G; Kretzler, Matthias; Wanke, Rüdiger; Pavenstädt, Hermann; Kerjaschki, Dontscho; Cohen, Clemens D; Hall, Michael N; Rüegg, Markus A; Inoki, Ken; Walz, Gerd; Huber, Tobias B.

in: J CLIN INVEST, Jahrgang 121, Nr. 6, 01.06.2011, S. 2197-209.

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

Harvard

Gödel, M, Hartleben, B, Herbach, N, Liu, S, Zschiedrich, S, Lu, S, Debreczeni-Mór, A, Lindenmeyer, MT, Rastaldi, M-P, Hartleben, G, Wiech, T, Fornoni, A, Nelson, RG, Kretzler, M, Wanke, R, Pavenstädt, H, Kerjaschki, D, Cohen, CD, Hall, MN, Rüegg, MA, Inoki, K, Walz, G & Huber, TB 2011, 'Role of mTOR in podocyte function and diabetic nephropathy in humans and mice', J CLIN INVEST, Jg. 121, Nr. 6, S. 2197-209. https://doi.org/10.1172/JCI44774

APA

Gödel, M., Hartleben, B., Herbach, N., Liu, S., Zschiedrich, S., Lu, S., Debreczeni-Mór, A., Lindenmeyer, M. T., Rastaldi, M-P., Hartleben, G., Wiech, T., Fornoni, A., Nelson, R. G., Kretzler, M., Wanke, R., Pavenstädt, H., Kerjaschki, D., Cohen, C. D., Hall, M. N., ... Huber, T. B. (2011). Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J CLIN INVEST, 121(6), 2197-209. https://doi.org/10.1172/JCI44774

Vancouver

Gödel M, Hartleben B, Herbach N, Liu S, Zschiedrich S, Lu S et al. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J CLIN INVEST. 2011 Jun 1;121(6):2197-209. https://doi.org/10.1172/JCI44774

Bibtex

@article{c15cab0cc3c8405182d7a7d955986433,
title = "Role of mTOR in podocyte function and diabetic nephropathy in humans and mice",
abstract = "Chronic glomerular diseases, associated with renal failure and cardiovascular morbidity, represent a major health issue. However, they remain poorly understood. Here we have reported that tightly controlled mTOR activity was crucial to maintaining glomerular podocyte function, while dysregulation of mTOR facilitated glomerular diseases. Genetic deletion of mTOR complex 1 (mTORC1) in mouse podocytes induced proteinuria and progressive glomerulosclerosis. Furthermore, simultaneous deletion of both mTORC1 and mTORC2 from mouse podocytes aggravated the glomerular lesions, revealing the importance of both mTOR complexes for podocyte homeostasis. In contrast, increased mTOR activity accompanied human diabetic nephropathy, characterized by early glomerular hypertrophy and hyperfiltration. Curtailing mTORC1 signaling in mice by genetically reducing mTORC1 copy number in podocytes prevented glomerulosclerosis and significantly ameliorated the progression of glomerular disease in diabetic nephropathy. These results demonstrate the requirement for tightly balanced mTOR activity in podocyte homeostasis and suggest that mTOR inhibition can protect podocytes and prevent progressive diabetic nephropathy.",
keywords = "Adaptor Proteins, Signal Transducing, Adult, Animals, Carrier Proteins, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Disease Progression, Gene Dosage, Genetic Predisposition to Disease, Humans, Kidney Glomerulus, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Mice, Knockout, Mice, Transgenic, Multiprotein Complexes, Nephrosis, Lipoid, Podocytes, Proteins, Proteinuria, Sirolimus, TOR Serine-Threonine Kinases, Trans-Activators, Transcription Factors",
author = "Markus G{\"o}del and Bj{\"o}rn Hartleben and Nadja Herbach and Shuya Liu and Stefan Zschiedrich and Shun Lu and Andrea Debreczeni-M{\'o}r and Lindenmeyer, {Maja T} and Maria-Pia Rastaldi and G{\"o}tz Hartleben and Thorsten Wiech and Alessia Fornoni and Nelson, {Robert G} and Matthias Kretzler and R{\"u}diger Wanke and Hermann Pavenst{\"a}dt and Dontscho Kerjaschki and Cohen, {Clemens D} and Hall, {Michael N} and R{\"u}egg, {Markus A} and Ken Inoki and Gerd Walz and Huber, {Tobias B}",
year = "2011",
month = jun,
day = "1",
doi = "10.1172/JCI44774",
language = "English",
volume = "121",
pages = "2197--209",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

RIS

TY - JOUR

T1 - Role of mTOR in podocyte function and diabetic nephropathy in humans and mice

AU - Gödel, Markus

AU - Hartleben, Björn

AU - Herbach, Nadja

AU - Liu, Shuya

AU - Zschiedrich, Stefan

AU - Lu, Shun

AU - Debreczeni-Mór, Andrea

AU - Lindenmeyer, Maja T

AU - Rastaldi, Maria-Pia

AU - Hartleben, Götz

AU - Wiech, Thorsten

AU - Fornoni, Alessia

AU - Nelson, Robert G

AU - Kretzler, Matthias

AU - Wanke, Rüdiger

AU - Pavenstädt, Hermann

AU - Kerjaschki, Dontscho

AU - Cohen, Clemens D

AU - Hall, Michael N

AU - Rüegg, Markus A

AU - Inoki, Ken

AU - Walz, Gerd

AU - Huber, Tobias B

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Chronic glomerular diseases, associated with renal failure and cardiovascular morbidity, represent a major health issue. However, they remain poorly understood. Here we have reported that tightly controlled mTOR activity was crucial to maintaining glomerular podocyte function, while dysregulation of mTOR facilitated glomerular diseases. Genetic deletion of mTOR complex 1 (mTORC1) in mouse podocytes induced proteinuria and progressive glomerulosclerosis. Furthermore, simultaneous deletion of both mTORC1 and mTORC2 from mouse podocytes aggravated the glomerular lesions, revealing the importance of both mTOR complexes for podocyte homeostasis. In contrast, increased mTOR activity accompanied human diabetic nephropathy, characterized by early glomerular hypertrophy and hyperfiltration. Curtailing mTORC1 signaling in mice by genetically reducing mTORC1 copy number in podocytes prevented glomerulosclerosis and significantly ameliorated the progression of glomerular disease in diabetic nephropathy. These results demonstrate the requirement for tightly balanced mTOR activity in podocyte homeostasis and suggest that mTOR inhibition can protect podocytes and prevent progressive diabetic nephropathy.

AB - Chronic glomerular diseases, associated with renal failure and cardiovascular morbidity, represent a major health issue. However, they remain poorly understood. Here we have reported that tightly controlled mTOR activity was crucial to maintaining glomerular podocyte function, while dysregulation of mTOR facilitated glomerular diseases. Genetic deletion of mTOR complex 1 (mTORC1) in mouse podocytes induced proteinuria and progressive glomerulosclerosis. Furthermore, simultaneous deletion of both mTORC1 and mTORC2 from mouse podocytes aggravated the glomerular lesions, revealing the importance of both mTOR complexes for podocyte homeostasis. In contrast, increased mTOR activity accompanied human diabetic nephropathy, characterized by early glomerular hypertrophy and hyperfiltration. Curtailing mTORC1 signaling in mice by genetically reducing mTORC1 copy number in podocytes prevented glomerulosclerosis and significantly ameliorated the progression of glomerular disease in diabetic nephropathy. These results demonstrate the requirement for tightly balanced mTOR activity in podocyte homeostasis and suggest that mTOR inhibition can protect podocytes and prevent progressive diabetic nephropathy.

KW - Adaptor Proteins, Signal Transducing

KW - Adult

KW - Animals

KW - Carrier Proteins

KW - Diabetes Mellitus, Experimental

KW - Diabetic Nephropathies

KW - Disease Progression

KW - Gene Dosage

KW - Genetic Predisposition to Disease

KW - Humans

KW - Kidney Glomerulus

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Inbred ICR

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Multiprotein Complexes

KW - Nephrosis, Lipoid

KW - Podocytes

KW - Proteins

KW - Proteinuria

KW - Sirolimus

KW - TOR Serine-Threonine Kinases

KW - Trans-Activators

KW - Transcription Factors

U2 - 10.1172/JCI44774

DO - 10.1172/JCI44774

M3 - SCORING: Journal article

C2 - 21606591

VL - 121

SP - 2197

EP - 2209

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 6

ER -