| Full text | |
| Author(s): Show less - |
Mesnard, Laurent
[1, 2]
;
Rafat, Cedric
[1, 2]
;
Vandermeersch, Sophie
[1]
;
Hertig, Alexandre
[1, 2]
;
Cathelin, Dominique
[1]
;
Xu-Dubois, Yi-Chun
[1]
;
Jouanneau, Chantal
[1]
;
Keller, Alexandre Castro
[3, 4]
;
Ribeil, Jean-Antoine
[4, 5]
;
Leite-de-Moraes, Maria C.
[4]
;
Rondeau, Eric
[1, 2]
Total Authors: 11
|
| Affiliation: | [1] Univ Paris 06, INSERM, UMR S702, Hop Tenon, F-75020 Paris - France
[2] Univ Paris 06, Hop Tenon, APHP, F-75020 Paris - France
[3] Univ Fed Sao Paulo, Div Nephrol, Sao Paulo - Brazil
[4] Hop Necker Enfants Malad, CNRS, UMR 8147, Paris - France
[5] Hop Necker Enfants Malad, APHP, Fac Med Rene Descartes, Dept Biotherapie, Paris - France
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | FASEB JOURNAL; v. 25, n. 10, p. 3543-3553, OCT 2011. |
| Web of Science Citations: | 6 |
| Abstract | |
During human glomerulonephritis, the severity of injuries correlates with glomerular fibrin deposits, which are tightly regulated by the intraglomerular fibrinolytic system. Here, we evaluated the role of vitronectin (VTN; also known as complement S protein), the principal cofactor of the plasminogen activator inhibitor-1 (PAI-1), in a mouse model of acute glomerulonephritis. We found that in mice subjected to nephrotoxic serum, the absence of VTN resulted in a lower glomerular PAI-1 activity and a higher glomerular fibrinolytic activity. Challenged VTN(-/-) mice displayed significantly less fibrin deposits, proteinuria, and renal failure than their wild-type counterparts. Notably, this protective effect afforded by VTN deficiency was still observed after a C3 depletion. Finally, the injection of VTN(+/+) serum in VTN(-/-) mice induced the glomerular deposition of VTN, increased PAI-1 deposition, decreased glomerular fibrinolytic activity, and aggravated glomerular injury. As in mice, abundant glomerular VTN deposits were also observed in patients with severe glomerulonephritis. Here, we show that plasma-exchange therapy, admittedly beneficial in this clinical context, induces a significant depletion in circulating VTN, which might modulate PAI-1 activity locally and accelerate the clearance of fibrin deposits in the glomeruli. Collectively, these results demonstrate that VTN exerts a deleterious role independently from complement, by directing PAI-dependent fibrinolysis in the glomerular compartment.-Mesnard, L., Rafat, C., Vandermeersch, S., Hertig, A., Cathelina, D., Xu-Dubois, Y. -C., Jouanneau, C., Castro Keller, A., Ribeil, J. -A., Leite-de-Moraes, M. C., Rondeau, E. Vitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritis. FASEB J. 25, 3543-3553 (2011). www.fasebj.org (AU) | |
| FAPESP's process: | 07/07120-0 - The role of invariant natural killer T cells in the development of glomerulonephritis: mechanisms and perspectives |
| Grantee: | Alexandre de Castro Keller |
| Support Opportunities: | Research Grants - Young Investigators Grants |