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DC Field | Value | Language |
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dc.contributor.author | Denton K.M. | en |
dc.contributor.author | Bertram J.F. | en |
dc.contributor.author | Ricardo S.D. | en |
dc.contributor.author | Kerr P.G. | en |
dc.contributor.author | Furic L. | en |
dc.contributor.author | Nikolic-Paterson D.J. | en |
dc.contributor.author | Huber T.B. | en |
dc.contributor.author | Puelles V.G. | en |
dc.contributor.author | Van Der Wolde J.W. | en |
dc.contributor.author | Wanner N. | en |
dc.contributor.author | Scheppach M.W. | en |
dc.contributor.author | Cullen-McEwen L.A. | en |
dc.contributor.author | Bork T. | en |
dc.contributor.author | Lindenmeyer M.T. | en |
dc.contributor.author | Gernhold L. | en |
dc.contributor.author | Wong M.N. | en |
dc.contributor.author | Braun F. | en |
dc.contributor.author | Cohen C.D. | en |
dc.contributor.author | Kett M.M. | en |
dc.contributor.author | Kuppe C. | en |
dc.contributor.author | Kramann R. | en |
dc.contributor.author | Saritas T. | en |
dc.contributor.author | Van Roeyen C.R. | en |
dc.contributor.author | Moeller M.J. | en |
dc.contributor.author | Tribolet L. | en |
dc.contributor.author | Rebello R. | en |
dc.contributor.author | Sun Y.B. | en |
dc.contributor.author | Li J. | en |
dc.contributor.author | Muller-Newen G. | en |
dc.contributor.author | Hughson M.D. | en |
dc.contributor.author | Hoy W.E. | en |
dc.contributor.author | Person F. | en |
dc.contributor.author | Wiech T. | en |
dc.date.accessioned | 2021-05-14T12:11:11Z | en |
dc.date.available | 2021-05-14T12:11:11Z | en |
dc.date.copyright | 2019 | en |
dc.date.created | 20191003 | en |
dc.date.issued | 2019-10-03 | en |
dc.identifier.citation | JCI Insight. 4 (18) (no pagination), 2019. Article Number: e99271. Date of Publication: 19 Sep 2019. | en |
dc.identifier.issn | 2379-3708 (electronic) | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/35982 | en |
dc.description.abstract | The cellular origins of glomerulosclerosis involve activation of parietal epithelial cells (PECs) and progressive podocyte depletion. While mammalian target of rapamycin-mediated (mTORmediated) podocyte hypertrophy is recognized as an important signaling pathway in the context of glomerular disease, the role of podocyte hypertrophy as a compensatory mechanism preventing PEC activation and glomerulosclerosis remains poorly understood. In this study, we show that glomerular mTOR and PEC activation-related genes were both upregulated and intercorrelated in biopsies from patients with focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, suggesting both compensatory and pathological roles. Advanced morphometric analyses in murine and human tissues identified podocyte hypertrophy as a compensatory mechanism aiming to regulate glomerular functional integrity in response to somatic growth, podocyte depletion, and even glomerulosclerosis - all of this in the absence of detectable podocyte regeneration. In mice, pharmacological inhibition of mTOR signaling during acute podocyte loss impaired hypertrophy of remaining podocytes, resulting in unexpected albuminuria, PEC activation, and glomerulosclerosis. Exacerbated and persistent podocyte hypertrophy enabled a vicious cycle of podocyte loss and PEC activation, suggesting a limit to its beneficial effects. In summary, our data highlight a critical protective role of mTOR-mediated podocyte hypertrophy following podocyte loss in order to preserve glomerular integrity, preventing PEC activation and glomerulosclerosis.Copyright © 2019, American Society for Clinical Investigation. | en |
dc.language | en | en |
dc.language | English | en |
dc.publisher | American Society for Clinical Investigation | en |
dc.title | MTOR-mediated podocyte hypertrophy regulates glomerular integrity in mice and humans. | en |
dc.type | Article | en |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1172/jci.insight.99271 | en |
dc.publisher.place | United States | en |
dc.identifier.pubmedid | 31534053 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31534053] | en |
dc.identifier.source | 2002964037 | en |
dc.identifier.institution | (Puelles, Van Der Wolde, Cullen-McEwen, Tribolet, Rebello, Sun, Li, Ricardo, Bertram) Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia (Puelles, Kerr, Nikolic-Paterson) Department of Nephrology, Monash Health, Melbourne, Australia (Puelles, Kerr, Nikolic-Paterson) Center for Inflammatory Diseases, Monash University, Melbourne, Australia (Puelles, Wanner, Lindenmeyer, Gernhold, Wong, Braun, Huber) III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrase 52, Gebaude N27, Hamburg 20246, Germany (Scheppach, Bork) Renal Division, University Medical Center Freiburg, Freiburg, Germany (Cohen) Nephrological Center Medical Clinic and Polyclinic IV, University of Munich, Munich, Germany (Kett, Denton) Cardiovascular Program, Monash Biomedicine Discovery Institute, Department of Physiology, Monash University, Melbourne, Australia (Kuppe, Kramann, Saritas, Van Roeyen, Moeller) Department of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany (Muller-Newen) Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany (Hughson) Department of Pathology, University of Mississippi Medical Center, Jackson, MI, United States (Hoy) Centre for Chronic Disease, University of Queensland, Brisbane, QLD, Australia (Person, Wiech) Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Furic) Prostate Cancer Translational Research Laboratory, Peter MacCallum Cancer Centre, Australia (Furic) Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia (Furic) Cancer Program, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia | en |
dc.description.address | V.G. Puelles, III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrase 52, Gebaude N27, Hamburg 20246, Germany. E-mail: victor.puellesrodriguez@monash.edu | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2019 Elsevier B.V., All rights reserved. | en |
dc.identifier.authoremail | Bertram J.F.; john.bertram@monash.edu Nikolic-Paterson D.J.; david.nikolic-paterson@monash.edu Puelles V.G.; victor.puellesrodriguez@monash.edu Huber T.B.; t.huber@uke.de | en |
dc.description.grant | No: 616891 Organization: *European Research Council* No: 677448 Organization: *European Research Council* No: CA1084546 Organization: *Cancer Australia* No: MCRF16007 Organization: *Victorian Cancer Agency* | en |
item.fulltext | No Fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | Article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
crisitem.author.dept | Nephrology | - |
crisitem.author.dept | Nephrology | - |
Appears in Collections: | Articles |
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