Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response, and development. Total-body deletion of the two Pparg alleles provoked generalized lipoatrophy along with severe type 2 diabetes. Herein, we explor...

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Main Authors: Barbara Toffoli, Federica Gilardi, Carine Winkler, Magnus Soderberg, Laura Kowalczuk, Yvan Arsenijevic, Krister Bamberg, Olivier Bonny, Béatrice Desvergne
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5300244?pdf=render
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author Barbara Toffoli
Federica Gilardi
Carine Winkler
Magnus Soderberg
Laura Kowalczuk
Yvan Arsenijevic
Krister Bamberg
Olivier Bonny
Béatrice Desvergne
author_facet Barbara Toffoli
Federica Gilardi
Carine Winkler
Magnus Soderberg
Laura Kowalczuk
Yvan Arsenijevic
Krister Bamberg
Olivier Bonny
Béatrice Desvergne
author_sort Barbara Toffoli
collection DOAJ
description Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response, and development. Total-body deletion of the two Pparg alleles provoked generalized lipoatrophy along with severe type 2 diabetes. Herein, we explore the appearance and development of structural and functional alterations of the kidney, comparing Pparg null-mice to their littermate controls (carrying Pparg floxed alleles). We show that renal hypertrophy and functional alterations with increased glucosuria and albuminuria are already present in 3 weeks-old Pparg null-mice. Renal insufficiency with decreased creatinine clearance progress at 7 weeks of age, with the advance of the type 2 diabetes. At 52 weeks of age, these alterations are accompanied by signs of fibrosis and mesangial expansion. More intriguingly, aged Pparg null-mice concomitantly present an anti-phospholipid syndrome (APS), characterized by the late appearance of microthrombi and a mesangioproliferative pattern of glomerular injury, associated with significant plasmatic levels of anti-β2- glycoprotein1 antibodies and renal deposition of IgG, IgM, and C3. Thus, in line with the role of PPARγ in metabolic homeostasis, Pparg null-mice first represent a potent model for studying the initiation and the development of diabetic nephropathy. Second, and in relation with the important PPARγ activity in inflammation and in immune system, these mice also highlight a new role for PPARγ signaling in the promotion of APS, a syndrome whose pathogenesis is poorly known and whose current treatment is limited to prevention of thrombosis events.
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spelling doaj.art-4ff6c1385d6148348a565d93def9243d2022-12-21T19:00:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017147410.1371/journal.pone.0171474Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.Barbara ToffoliFederica GilardiCarine WinklerMagnus SoderbergLaura KowalczukYvan ArsenijevicKrister BambergOlivier BonnyBéatrice DesvergnePeroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response, and development. Total-body deletion of the two Pparg alleles provoked generalized lipoatrophy along with severe type 2 diabetes. Herein, we explore the appearance and development of structural and functional alterations of the kidney, comparing Pparg null-mice to their littermate controls (carrying Pparg floxed alleles). We show that renal hypertrophy and functional alterations with increased glucosuria and albuminuria are already present in 3 weeks-old Pparg null-mice. Renal insufficiency with decreased creatinine clearance progress at 7 weeks of age, with the advance of the type 2 diabetes. At 52 weeks of age, these alterations are accompanied by signs of fibrosis and mesangial expansion. More intriguingly, aged Pparg null-mice concomitantly present an anti-phospholipid syndrome (APS), characterized by the late appearance of microthrombi and a mesangioproliferative pattern of glomerular injury, associated with significant plasmatic levels of anti-β2- glycoprotein1 antibodies and renal deposition of IgG, IgM, and C3. Thus, in line with the role of PPARγ in metabolic homeostasis, Pparg null-mice first represent a potent model for studying the initiation and the development of diabetic nephropathy. Second, and in relation with the important PPARγ activity in inflammation and in immune system, these mice also highlight a new role for PPARγ signaling in the promotion of APS, a syndrome whose pathogenesis is poorly known and whose current treatment is limited to prevention of thrombosis events.http://europepmc.org/articles/PMC5300244?pdf=render
spellingShingle Barbara Toffoli
Federica Gilardi
Carine Winkler
Magnus Soderberg
Laura Kowalczuk
Yvan Arsenijevic
Krister Bamberg
Olivier Bonny
Béatrice Desvergne
Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.
PLoS ONE
title Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.
title_full Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.
title_fullStr Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.
title_full_unstemmed Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.
title_short Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.
title_sort nephropathy in pparg null mice highlights pparγ systemic activities in metabolism and in the immune system
url http://europepmc.org/articles/PMC5300244?pdf=render
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