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- Title
Functional Expression of the Renin Angiotensin System in Human Podocytes.
- Authors
Liebau, M. C.; Bek, M. J.; Witherden, I.; Saleem, M. A.; Pavenstädt, H.; Fischer, K. -G.
- Abstract
Objective: 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 diseases. 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 inhibition of a local renin angiotensin system (RAS) in podocytes. The knowledge of expression and function of a local RAS in podocytes is limited. Results: We demonstrate functional expression of key components of the RAS in differentiated human podocytes: Podocytes express mRNA for angiotensinogen, renin, ACE type 1, and both the AT1 and AT2 angiotensin receptor subtype. In Western blot and immunofluorescence experiments, AT1 receptor expression was prominent, whereas the expression level of the AT2 receptor was lower. In human kidney cortex, only AT1 receptor expression was detected. Angiotensin II (Ang II) induced a concentration-dependent increase of the cytosolic Ca2+ concentration (EC50: 60 nM) via AT1 receptors in differentiated human podocytes, which was reversibly blocked by the AT1 receptor antagonist losartan. Ang II did not increase cAMP. Finally, Ang II secretion was detected, which was not blocked by the ACEI captopril. Conclusions: We speculate that ACEI and ARB exert their beneficial effects in part by inhibiting a local RAS in podocytes. Further experiments are required to identify the underlying molecular mechanism of podocyte protection.
- Subjects
ACE inhibitors; RENIN-angiotensin system; PROTEINURIA; GENE expression; MESSENGER RNA; SARALASIN; WESTERN immunoblotting
- Publication
Kidney & Blood Pressure Research, 2004, Vol 27, Issue 5/6, p289
- ISSN
1420-4096
- Publication type
Article