Nephrol Dial Transplant (2001) 16: 34-39
© 2001 European Renal Association-European Dialysis and Transplant Association
Up-regulation of endoglin, a TGF-ß-binding protein, in rats with experimental renal fibrosis induced by renal mass reduction
Instituto ‘Reina Sofía’ de Investigación Nefrológica, Departamento de Fisiología y Farmacología, 1 Departamento de Anatomía e Histología Humanas, Universidad de Salamanca, Salamanca, 3 Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain and 2 The Center for Molecular Medicine, Maine Medical Center Research Institute, South Portland, Maine, USA
Background. The central process in chronic renal failure is the progressive accumulation of extracellular matrix in the glomeruli and in the tubulo-interstitial space, resulting in renal fibrosis. Transforming growth factor-ß1 (TGF-ß1) up-regulation plays a major role in the genesis of renal fibrosis. Endoglin is a membrane glycoprotein that binds TGF-ß1 and TGF-ß3 with high affinity. An increased level of endoglin immunostaining has been demonstrated previously in biopsies from patients with chronic progressive renal disease. We have assessed the expression of endoglin in the rat 5/6th renal mass reduction (RMR) model.
Methods. One, 3 and 5 months after RMR, mean arterial pressure and renal function were measured, animals were sacrificed, renal fibrosis was evaluated quantitatively and the expression of endoglin was assessed by western blot, northern blot and immunohistochemistry.
Results. RMR induced a progressive increase in mean arterial pressure and urinary protein excretion. Renal corpuscular area, and mesangial and interstitial fibrosis increased with time after RMR. Immunohistochemical staining for endoglin demonstrated its expression mainly on the endothelial surface of major vessels. In kidneys 1 and 3 months after RMR, the expression of endoglin in renal corpuscles was limited to Bowman's parietal epithelium. In rats 5 months after RMR, the immunoexpression in glomerular endothelium was more marked. Northern blot analysis revealed that rats with RMR showed an increase in the expression of mRNA for endoglin, only at 5 months after RMR. Western blot analysis gave a different time course: a marked increase in the first month, a decrease in the 3rd month and a further increase in the 5th month after RMR.
Conclusions. The present study demonstrates increased endoglin expression in rats with severe hypertension and renal damage. This increased endoglin expression coincides with the period of higher renal damage and renal dysfunction.
Keywords: chronic renal failure; endoglin; glomerulosclerosis; renal mass reduction; transforming growth factor-ß; tubulo-tubulo-interstitial fibrosis
Correspondence and offprint requests to: J. M. López-Novoa, Departamento de Fisiología y Farmacología, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
A. Rodríguez-Peña and M. Prieto contributed equally to this work.
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