Endoglin Upregulation During Experimental Renal Interstitial Fibrosis in Mice

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2002-11, Vol.40 (5), p.713-720
• Main Authors: Rodríguez-Peña, Ana, Eleno, Nélida, Düwell, Anette, Arévalo, Miguel, Pérez-Barriocanal, Fernando, Flores, Olga, Docherty, Neil, Bernabeu, Carmelo, Letarte, Michelle, López-Novoa, José M
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD; Blotting, Northern; Blotting, Western; Collagen - genetics; Collagen - metabolism; Disease Models, Animal; Endoglin; Fibronectins - genetics; Fibronectins - metabolism; Fibrosis - complications; Fibrosis - metabolism; Fibrosis - pathology; Heterozygote; Immunohistochemistry; Kidney - chemistry; Kidney - metabolism; Kidney - pathology; Kidney Diseases - complications; Kidney Diseases - metabolism; Kidney Diseases - pathology; Ligation; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Receptors, Cell Surface; RNA, Messenger - analysis; RNA, Messenger - metabolism; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1; Up-Regulation; Ureter; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.0000037429.73954.27

ABSTRACT—The goal of the present study was to evaluate the role of endoglin, a transforming growth factor-β1 (TGF-β1) 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 α2(I) and α1(IV) collagen, fibronectin, and TGF-β1 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-β1 in the renal fibrosis process.