Aim. In diabetes glomerular capillary hypertension induces an abnormal mechanical stretching of glomerular resident cells that contributes to glomerular injury Podocytes form an integral part of the glomerular filtration barrier, participate in glomerular basement membrane formation, and they are believed to play a key role in the pathogenesis of diabetic nephropathy. The aim of this study was to assess in vitro in podocytes the effect of mechanical stretch, mimicking in vitro the hemodynamic insult of glomerular hypertension, on fibronectin and TGF-beta 1 expression. Methods. Human cultured podocytes were exposed to mechanical stretching using a Stress Unit for various time periods. Fibronectin and TGF-beta 1 protein levels were measured by immunoblotting on total protein extracts. To investigate the potential role of TGF-beta 1 as a mediator of stretch-induced fibronectin, in selected experiments, cells were exposed to stretch in the presence of either a specific anti-TGF-beta 1 blocking antibody or a control IgG. Results. Stretch induced a significant increase in fibronectin production after 3, 5, and 7 days of exposure. A peak with a 7-fold increase in fibronectin production as compared to control was observed at 72 hours. Stretch also induced a significant rise in TGF-beta 1 protein levels at 12 hours. Finally, stretch-induced fibronectin overproduction at 72 hours was completely prevented by TGF-beta 1 blockade. Conclusion. Mechanical stretch induces fibronectin production in podocytes by a TGF-beta 1-dependent mechanism.
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