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

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State: Public
Version: Final published version
Serval ID
serval:BIB_5AA23F6A13A3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.
Journal
PLoS One
Author(s)
Toffoli B., Gilardi F., Winkler C., Soderberg M., Kowalczuk L., Arsenijevic Y., Bamberg K., Bonny O., Desvergne B.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
12
Number
2
Pages
e0171474
Language
english
Abstract
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.

Pubmed
Web of science
Open Access
Yes
Create date
21/02/2017 20:13
Last modification date
17/09/2020 9:18
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