| First Author | Toffoli B | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 2 | Pages | e0171474 |
| PubMed ID | 28182703 | Mgi Jnum | J:246755 |
| Mgi Id | MGI:5919296 | Doi | 10.1371/journal.pone.0171474 |
| Citation | Toffoli B, et al. (2017) Nephropathy in Pparg-null mice highlights PPARgamma systemic activities in metabolism and in the immune system. PLoS One 12(2):e0171474 |
| abstractText | Peroxisome proliferator-activated receptor gamma (PPARgamma) 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-beta2- glycoprotein1 antibodies and renal deposition of IgG, IgM, and C3. Thus, in line with the role of PPARgamma 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 PPARgamma activity in inflammation and in immune system, these mice also highlight a new role for PPARgamma signaling in the promotion of APS, a syndrome whose pathogenesis is poorly known and whose current treatment is limited to prevention of thrombosis events. |
