This Article Full Text Full Text (PDF) All Versions of this Article: 40/5/713    most recent 01.HYP.0000037429.73954.27v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rodríguez-Peña, A. Articles by López-Novoa, J. M. Search for Related Content PubMed PubMed Citation Articles by Rodríguez-Peña, A. Articles by López-Novoa, J. M. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Kidney Diseases Related Collections Animal models of human disease Genetically altered mice

(Hypertension. 2002;40:713.)
© 2002 American Heart Association, Inc.

Scientific Contributions

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; 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.

Correspondence to José M. López-Novoa, PhD, Departamento de Fisiología y Farmacología, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain. E-mail jmlnovoa{at}gugu.usal.es

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

This article has been cited by other articles:

				M. Jerkic, J. V. Rivas-Elena, J. F. Santibanez, M. Prieto, A. Rodriguez-Barbero, F. Perez-Barriocanal, M. Pericacho, M. Arevalo, C. P.H. Vary, M. Letarte, et al. Endoglin Regulates Cyclooxygenase-2 Expression and Activity Circ. Res., August 4, 2006; 99(3): 248 - 256. [Abstract] [Full Text] [PDF]

				N. G. Docherty, J. M. Lopez-Novoa, M. Arevalo, A. Duwel, A. Rodriguez-Pena, F. Perez-Barriocanal, C. Bernabeu, and N. Eleno Endoglin regulates renal ischaemia-reperfusion injury Nephrol. Dial. Transplant., August 1, 2006; 21(8): 2106 - 2119. [Abstract] [Full Text] [PDF]

				C. Roufosse, G. Bou-Gharios, E. Prodromidi, C. Alexakis, R. Jeffery, S. Khan, W. R. Otto, J. Alter, R. Poulsom, and H. T. Cook Bone Marrow-Derived Cells Do Not Contribute Significantly to Collagen I Synthesis in a Murine Model of Renal Fibrosis J. Am. Soc. Nephrol., March 1, 2006; 17(3): 775 - 782. [Abstract] [Full Text] [PDF]

				N. G. Docherty, O. E. O'Sullivan, D. A. Healy, J. M. Fitzpatrick, and R. W. G. Watson Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction Am J Physiol Renal Physiol, January 1, 2006; 290(1): F4 - F13. [Abstract] [Full Text] [PDF]

				K. Chen, J. L. Mehta, D. Li, L. Joseph, and J. Joseph Transforming Growth Factor {beta} Receptor Endoglin Is Expressed in Cardiac Fibroblasts and Modulates Profibrogenic Actions of Angiotensin II Circ. Res., December 10, 2004; 95(12): 1167 - 1173. [Abstract] [Full Text] [PDF]

				D. M. Sadlier, S. B. Connolly, N. E. Kieran, S. Roxburgh, D. P. Brazil, L. Kairaitis, Y. Wang, D. C. H. Harris, P. Doran, and H. R. Brady Sequential Extracellular Matrix-focused and Baited-global Cluster Analysis of Serial Transcriptomic Profiles Identifies Candidate Modulators of Renal Tubulointerstitial Fibrosis in Murine Adriamycin-induced Nephropathy J. Biol. Chem., July 9, 2004; 279(28): 29670 - 29680. [Abstract] [Full Text] [PDF]