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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/F379    most recent 00019.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Westerweel, P. E. Articles by Verhaar, M. C. Search for Related Content PubMed PubMed Citation Articles by Westerweel, P. E. Articles by Verhaar, M. C.

Amelioration of anti-Thy1-glomerulonephritis by PPAR- agonism without increase of endothelial progenitor cell homing

Departments of ¹Vascular Medicine, ²Pathology, and ³Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands

Submitted 11 January 2007 ; accepted in final form 4 December 2007

Impaired glomerular endothelial integrity is pivotal in various renal diseases and depends on both the degree of glomerular endothelial injury and the effectiveness of glomerular endothelial repair. Glomerular endothelial repair is, in part, mediated by bone marrow-derived endothelial progenitor cells. Peroxisome proliferator activated receptor- (PPAR-) agonists have therapeutic actions independent of their insulin-sensitizing effects, including enhancement of endothelial progenitor cell function and differentiation. We evaluated the effect of PPAR- agonist rosiglitazone (4 mg·kg^–1·day^–1) on the course of anti-Thy1-glomerulonephritis in rats. Rosiglitazone limited the development of proteinuria and prevented plasma urea elevation (8.1 ± 0.4 vs. 12.5 ± 1.1 mmol/l, P = 0.002). Histologically, inflammatory cell influx was not affected, but rosiglitazone-treated rats did show fewer microaneurysmatic glomeruli on day 7 (26 ± 3 vs. 41 ± 5%, P = 0.01) and reduced activation of matrix production with reduced renal cortical transforming growth factor-β, plasminogen activator inhibitor type 1, and fibronectin-1 mRNA expression. However, bone marrow-derived endothelial cell glomerular incorporation was not enhanced (3.1 ± 0.4 vs. 3.6 ± 0.3 cells/glomerular cross section; P = 0.31). Rosiglitazone treatment in nonnephritic rats did not influence proteinuria, urea, or renal histology. In conclusion, treatment with PPAR- agonist rosiglitazone ameliorates the course of experimental glomerulonephritis in a nondiabetic model, but not through enhancing incorporation of bone marrow-derived endothelial cells in the glomerulus.

anti-Thy1-glomerulonephritis; peroxisome proliferator activated receptors; stem cell