nephrin and Aneurysm

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-gamma (PPAR-gamma) 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-gamma 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-beta, 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-gamma 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.

Topics: Aneurysm; Animals; Blood Pressure; Bone Marrow Transplantation; Cell Movement; Disease Models, Animal; Endothelial Cells; Extracellular Matrix; Fibronectins; Gene Expression; Glomerulonephritis, Membranous; Hypoglycemic Agents; Isoantibodies; Kidney Cortex; Kidney Glomerulus; Male; Membrane Proteins; Plasminogen Activator Inhibitor 1; PPAR gamma; Proteinuria; Rats; Rats, Inbred BN; Rosiglitazone; Stem Cells; Thiazolidinediones; Transforming Growth Factor beta; Urea