Published Online
on October 7, 2002

A more recent version of this article appeared on November 1, 2002

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Submitted on June 17, 2002
Revised on July 3, 2002

Endoglin Upregulation During Experimental Renal Interstitial Fibrosis in Mice

Ana Rodríguez-Peña; Nélida Eleno; Anette Düwell; Miguel Arévalo; Fernando Pérez-Barriocanal; Olga Flores; Neil Docherty; Carmelo Bernabeu; Michelle Letarte; and José M. López-Novoa^*

From Instituto "Reina Sofía" de Investigación Nefrológica, Departamento de Fisiología & Farmacología (A.R.-P., N.E., A.D., F.P.-B., O.F., N.D., J.M.L.-N.), and Departamento de Anatomía e Histología Humanas (M.A.), Universidad de Salamanca, Salamanca, Spain; Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.B.), Madrid, Spain; and Hospital for Sick Children and Department of Immunology, University of Toronto (M.L.), Toronto, Canada.

^* To whom correspondence should be addressed. E-mail: jmlnovoa{at}gugu.usal.es.

Abstract—The goal of the present study was to evaluate the role of endoglin, a transforming growth factor-ß1 (TGF-ß1) accessory receptor, in the pathogenesis of renal fibrosis. This was achieved by testing a model of tubulo-interstitial fibrosis induced by unilateral ureteral obstruction in endoglin heterozygous (Eng^+/-) mice. Northern and Western blot analysis revealed that endoglin expression in kidneys of these mice was significantly reduced compared with Eng^+/+ littermates. Pronounced interstitial fibrosis induced by ureteral obstruction was confirmed histologically by Masson's trichromic staining and by increased immunostaining for fibronectin and laminin without significant differences between Eng^+/- and Eng^+/+ mice. Ureteral obstruction induced significant increases in 2(I) and 1(IV) collagen, fibronectin, and TGF-ß1 mRNA levels, as well as in total kidney collagen but changes were similar in Eng^+/- and Eng^+/+ mouse kidneys. Ureteral obstruction also induced a 2-fold increase in endoglin mRNA levels in both Eng^+/+ mice and Eng^+/- mice, which was confirmed by Western blot analysis. Thus, the present study provides clear evidence that endoglin is upregulated in the kidneys of mice with interstitial fibrosis induced by unilateral ureteral ligation. However, Eng^+/- mice do not show any changes in the severity of renal disease induced in this model when compared with normal mice, suggesting that the absolute level of endoglin is not critical for the effects of TGF-ß1 in the renal fibrosis process.

Key words: collagen • renal disease • fibrosis • transforming growth factors

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