Research ExplorerPublicationsAlterations in the Ubiquitin Proteasome System in Persistent...

Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases

Standard

Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases. / Beeken, Maire; Lindenmeyer, Maja T; Blattner, Simone M; Radón, Victoria; Oh, Jun; Meyer, Tobias N; Hildebrand, Diana; Schlüter, Hartmut; Reinicke-Vogt, Anna; Knop, Jan-Hendrik; Vivekanandan-Giri, Anuradha; Münster, Silvia; Sachs, Marlies; Wiech, Thorsten; Pennathur, Subramaniam; Cohen, Clemens D; Kretzler, Matthias; Stahl, Rolf A K; Meyer-Schwesinger, Catherine.

In: J AM SOC NEPHROL, Vol. 25, No. 11, 2014, p. 2511-25.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Beeken, M, Lindenmeyer, MT, Blattner, SM, Radón, V, Oh, J, Meyer, TN, Hildebrand, D, Schlüter, H, Reinicke-Vogt, A, Knop, J-H, Vivekanandan-Giri, A, Münster, S, Sachs, M, Wiech, T, Pennathur, S, Cohen, CD, Kretzler, M, Stahl, RAK & Meyer-Schwesinger, C 2014, 'Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases', J AM SOC NEPHROL, vol. 25, no. 11, pp. 2511-25. https://doi.org/10.1681/ASN.2013050522

APA

Beeken, M., Lindenmeyer, M. T., Blattner, S. M., Radón, V., Oh, J., Meyer, T. N., Hildebrand, D., Schlüter, H., Reinicke-Vogt, A., Knop, J-H., Vivekanandan-Giri, A., Münster, S., Sachs, M., Wiech, T., Pennathur, S., Cohen, C. D., Kretzler, M., Stahl, R. A. K., & Meyer-Schwesinger, C. (2014). Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases. J AM SOC NEPHROL, 25(11), 2511-25. https://doi.org/10.1681/ASN.2013050522

Vancouver

Beeken M, Lindenmeyer MT, Blattner SM, Radón V, Oh J, Meyer TN et al. Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases. J AM SOC NEPHROL. 2014;25(11):2511-25. https://doi.org/10.1681/ASN.2013050522

Bibtex

@article{1339c7ff3b384ac191c8ba7a26112f88,
title = "Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases",
abstract = "Podocytes are the key cells affected in nephrotic glomerular kidney diseases, and they respond uniformly to injury with cytoskeletal rearrangement. In nephrotic diseases, such as membranous nephropathy and FSGS, persistent injury often leads to irreversible structural damage, whereas in minimal change disease, structural alterations are mostly transient. The factors leading to persistent podocyte injury are currently unknown. Proteolysis is an irreversible process and could trigger persistent podocyte injury through degradation of podocyte-specific proteins. We, therefore, analyzed the expression and functional consequence of the two most prominent proteolytic systems, the ubiquitin proteasome system (UPS) and the autophagosomal/lysosomal system, in persistent and transient podocyte injuries. We show that differential upregulation of both proteolytic systems occurs in persistent human and rodent podocyte injury. The expression of specific UPS proteins in podocytes differentiated children with minimal change disease from children with FSGS and correlated with poor clinical outcome. Degradation of the podocyte-specific protein α-actinin-4 by the UPS depended on oxidative modification in membranous nephropathy. Notably, the UPS was overwhelmed in podocytes during experimental glomerular disease, resulting in abnormal protein accumulation and compensatory upregulation of the autophagosomal/lysosomal system. Accordingly, inhibition of both proteolytic systems enhanced proteinuria in persistent nephrotic disease. This study identifies altered proteolysis as a feature of persistent podocyte injury. In the future, specific UPS proteins may serve as new biomarkers or therapeutic targets in persistent nephrotic syndrome.",
author = "Maire Beeken and Lindenmeyer, {Maja T} and Blattner, {Simone M} and Victoria Rad{\'o}n and Jun Oh and Meyer, {Tobias N} and Diana Hildebrand and Hartmut Schl{\"u}ter and Anna Reinicke-Vogt and Jan-Hendrik Knop and Anuradha Vivekanandan-Giri and Silvia M{\"u}nster and Marlies Sachs and Thorsten Wiech and Subramaniam Pennathur and Cohen, {Clemens D} and Matthias Kretzler and Stahl, {Rolf A K} and Catherine Meyer-Schwesinger",
year = "2014",
doi = "10.1681/ASN.2013050522",
language = "English",
volume = "25",
pages = "2511--25",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "11",

}

RIS

TY - JOUR

T1 - Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases

AU - Beeken, Maire

AU - Lindenmeyer, Maja T

AU - Blattner, Simone M

AU - Radón, Victoria

AU - Oh, Jun

AU - Meyer, Tobias N

AU - Hildebrand, Diana

AU - Schlüter, Hartmut

AU - Reinicke-Vogt, Anna

AU - Knop, Jan-Hendrik

AU - Vivekanandan-Giri, Anuradha

AU - Münster, Silvia

AU - Sachs, Marlies

AU - Wiech, Thorsten

AU - Pennathur, Subramaniam

AU - Cohen, Clemens D

AU - Kretzler, Matthias

AU - Stahl, Rolf A K

AU - Meyer-Schwesinger, Catherine

PY - 2014

Y1 - 2014

N2 - Podocytes are the key cells affected in nephrotic glomerular kidney diseases, and they respond uniformly to injury with cytoskeletal rearrangement. In nephrotic diseases, such as membranous nephropathy and FSGS, persistent injury often leads to irreversible structural damage, whereas in minimal change disease, structural alterations are mostly transient. The factors leading to persistent podocyte injury are currently unknown. Proteolysis is an irreversible process and could trigger persistent podocyte injury through degradation of podocyte-specific proteins. We, therefore, analyzed the expression and functional consequence of the two most prominent proteolytic systems, the ubiquitin proteasome system (UPS) and the autophagosomal/lysosomal system, in persistent and transient podocyte injuries. We show that differential upregulation of both proteolytic systems occurs in persistent human and rodent podocyte injury. The expression of specific UPS proteins in podocytes differentiated children with minimal change disease from children with FSGS and correlated with poor clinical outcome. Degradation of the podocyte-specific protein α-actinin-4 by the UPS depended on oxidative modification in membranous nephropathy. Notably, the UPS was overwhelmed in podocytes during experimental glomerular disease, resulting in abnormal protein accumulation and compensatory upregulation of the autophagosomal/lysosomal system. Accordingly, inhibition of both proteolytic systems enhanced proteinuria in persistent nephrotic disease. This study identifies altered proteolysis as a feature of persistent podocyte injury. In the future, specific UPS proteins may serve as new biomarkers or therapeutic targets in persistent nephrotic syndrome.

AB - Podocytes are the key cells affected in nephrotic glomerular kidney diseases, and they respond uniformly to injury with cytoskeletal rearrangement. In nephrotic diseases, such as membranous nephropathy and FSGS, persistent injury often leads to irreversible structural damage, whereas in minimal change disease, structural alterations are mostly transient. The factors leading to persistent podocyte injury are currently unknown. Proteolysis is an irreversible process and could trigger persistent podocyte injury through degradation of podocyte-specific proteins. We, therefore, analyzed the expression and functional consequence of the two most prominent proteolytic systems, the ubiquitin proteasome system (UPS) and the autophagosomal/lysosomal system, in persistent and transient podocyte injuries. We show that differential upregulation of both proteolytic systems occurs in persistent human and rodent podocyte injury. The expression of specific UPS proteins in podocytes differentiated children with minimal change disease from children with FSGS and correlated with poor clinical outcome. Degradation of the podocyte-specific protein α-actinin-4 by the UPS depended on oxidative modification in membranous nephropathy. Notably, the UPS was overwhelmed in podocytes during experimental glomerular disease, resulting in abnormal protein accumulation and compensatory upregulation of the autophagosomal/lysosomal system. Accordingly, inhibition of both proteolytic systems enhanced proteinuria in persistent nephrotic disease. This study identifies altered proteolysis as a feature of persistent podocyte injury. In the future, specific UPS proteins may serve as new biomarkers or therapeutic targets in persistent nephrotic syndrome.

U2 - 10.1681/ASN.2013050522

DO - 10.1681/ASN.2013050522

M3 - SCORING: Journal article

C2 - 24722446

VL - 25

SP - 2511

EP - 2525

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 11

ER -