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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/F710    most recent 00475.2004v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (23) Citing Articles via Google Scholar Google Scholar Articles by Liebau, M. C. Articles by Fischer, K.-G. Search for Related Content PubMed PubMed Citation Articles by Liebau, M. C. Articles by Fischer, K.-G.

Functional expression of the renin-angiotensin system in human podocytes

¹Department of Medicine, Division of Nephrology and General Medicine, University Hospital Freiburg, Freiburg; ²Department of Medicine D, Division of General Internal Medicine and Nephrology, University Hospital Münster, Münster; ³Department of Pathology, University of Freiburg, Freiburg; ⁴Department of Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany; and ⁵Children's Renal Unit and Academic Renal Unit, Southmead Hospital, University of Bristol, Bristol, United Kingdom

Submitted 3 January 2005 ; accepted in final form 19 September 2005

Experimental and clinical studies impressively demonstrate that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) significantly reduce proteinuria and retard progression of glomerular disease. The underlying intraglomerular mechanisms are not yet fully elucidated. As podocyte injury constitutes a critical step in the pathogenesis of glomerular proteinuria, beneficial effects of ACEI and ARB may partially result from interference with a local renin-angiotensin system (RAS) in podocytes. The knowledge of expression and function of a local RAS in podocytes is limited. In this study, we demonstrate functional expression of key components of the RAS in differentiated human podocytes: podocytes express mRNA for angiotensinogen, renin, ACE type 1, and the AT₁ and AT₂ angiotensin receptor subtypes. In Western blot experiments and immunostainings, expression of the AT₁ and AT₂ receptor was demonstrated both in differentiated human podocytes and in human kidney cortex. ANG II induced a concentration-dependent increase in cytosolic Ca²⁺ concentration via AT₁ receptors in differentiated human podocytes, whereas it did not increase cAMP. Furthermore, ANG II secretion was detected, which was blocked by neither the ACEI captopril nor the renin inhibitor remikiren nor the chymase inhibitor chymostatin. ANG II secretion of podocytes was not increased by mechanical stress. Finally, ANG II was found to increase staurosporine-induced apoptosis in podocytes. We speculate that ACEI and ARB exert their beneficial effects, in part, by interfering with a local RAS in podocytes. Further experiments are required to identify the underlying molecular mechanism(s) of podocyte protection.

cytosolic Ca²⁺; human; captopril; AT₁ receptor; AT₂ receptor; apoptosis; mechanical stress

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