These results suggest that downregulation of alpha3beta1 integrin expression, by mechanical forces or TGFbeta1, is per se sufficient to reduce podocyte adhesion. Apoptosis may represent a parallel important determinant of the podocyte loss from the GBM.

OBJECTIVEPatients with type 1 diabetes and microalbuminuria are at increased risk of cardiovascular disease (CVD). Abnormalities in vascular progenitor cells, which participate in vascular repair, may be implicated in this susceptibility.RESEARCH DESIGN AND METHODSWe studied the number and function of vascular progenitor cells in 22 type 1 diabetic patients with history of microalbuminuria (MA+) and 22 type 1 diabetic patients without history of microalbuminuria (MA−), of similar age, diabetes duration, glycemic control, renal function, and no history of CVD.RESULTSMA+ patients had lower circulating CD34+ and CD34+/CD133+ cell numbers compared with MA− patients (P < 0.006). In in vitro functional assays, MA+ patients had a significantly lower number of colony-forming units and impaired vascular endothelial growth factor (VEGF)-A–mediated tube formation, when compared with MA− patients (P < 0.01).CONCLUSIONSIn type 1 diabetic patients with microalbuminuria, a marker of microvascular injury and a risk factor for CVD, circulating vascular progenitor cell number is reduced and function is impaired.

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Backgrounds/Aims:Renal inflammation and nephrin downregulation contribute to albuminuria in diabetes. We studied, in streptozotocin-induced diabetic rats, the effect of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-γ agonist, on renal macrophage infiltration, MCP1, and nephrin expression in relation to albuminuria. Methods: We investigated control and diabetic rats treated or untreated with RSG. Animals were sacrificed at 1, 3, and 9 months. Renal MCP1 and nephrin expression were studied by immunoblotting, renal macrophage infiltration by immunohistochemistry, and albuminuria by ELISA. Electron microscopy was used to assess glomerular ultrastructural morphology. In vitroexperiments were conducted in isolated cultured rat glomeruli. Results: Glycaemic control was similar in diabetic rats treated and untreated with RSG, and blood pressure was comparable in all groups. RSG prevented diabetes-induced albuminuria at 9 months, and renal macrophage infiltration and MCP1 upregulation at 3 and 9 months. Diabetes-mediated nephrin downregulation was abolished by RSG. Diabetes-induced glomerulosclerosis, glomerular basement membrane thickening, and foot process fusion were not affected by RSG. In isolated glomeruli, MCP1 directly induced nephrin downregulation and this was prevented by RSG. RSG had no effect on nephrin expression. Conclusion: RSG prevents albuminuria and nephrin downregulation in experimental diabetes independently of glycaemic and blood pressure control. This effect likely occurs via correction of diabetes-induced inflammatory processes.