File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1152/ajprenal.00475.2004
- Scopus: eid_2-s2.0-33645577151
- WOS: WOS:000235082700019
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Functional expression of the renin-angiotensin system in human podocytes
Title | Functional expression of the renin-angiotensin system in human podocytes |
---|---|
Authors | |
Keywords | Apoptosis AT 2 receptor AT1 receptor Captopril Cytosolic Ca2+ Human Mechanical stress |
Issue Date | 2006 |
Citation | American Journal of Physiology - Renal Physiology, 2006, v. 290 n. 3, p. F710-F719 How to Cite? |
Abstract | 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 AT 1 and AT 2 angiotensin receptor subtypes. In Western blot experiments and immunostainings, expression of the AT 1 and AT 2 receptor was demonstrated both in differentiated human podocytes and in human kidney cortex. ANG II induced a concentration-dependent increase in cytosolic Ca 2+ concentration via AT 1 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. Copyright © 2006 the American Physiological Society. |
Persistent Identifier | http://hdl.handle.net/10722/195435 |
ISSN | |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Liebau, MC | - |
dc.contributor.author | Lang, D | - |
dc.contributor.author | Böhm, J | - |
dc.contributor.author | Endlich, N | - |
dc.contributor.author | Bek, MJ | - |
dc.contributor.author | Witherden, I | - |
dc.contributor.author | Mathieson, PW | - |
dc.contributor.author | Saleem, MA | - |
dc.contributor.author | Pavenstädt, H | - |
dc.contributor.author | Fischer, K-G | - |
dc.date.accessioned | 2014-02-28T06:12:09Z | - |
dc.date.available | 2014-02-28T06:12:09Z | - |
dc.date.issued | 2006 | - |
dc.identifier.citation | American Journal of Physiology - Renal Physiology, 2006, v. 290 n. 3, p. F710-F719 | - |
dc.identifier.issn | 0363-6127 | - |
dc.identifier.uri | http://hdl.handle.net/10722/195435 | - |
dc.description.abstract | 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 AT 1 and AT 2 angiotensin receptor subtypes. In Western blot experiments and immunostainings, expression of the AT 1 and AT 2 receptor was demonstrated both in differentiated human podocytes and in human kidney cortex. ANG II induced a concentration-dependent increase in cytosolic Ca 2+ concentration via AT 1 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. Copyright © 2006 the American Physiological Society. | - |
dc.language | eng | - |
dc.relation.ispartof | American Journal of Physiology - Renal Physiology | - |
dc.subject | Apoptosis | - |
dc.subject | AT 2 receptor | - |
dc.subject | AT1 receptor | - |
dc.subject | Captopril | - |
dc.subject | Cytosolic Ca2+ | - |
dc.subject | Human | - |
dc.subject | Mechanical stress | - |
dc.title | Functional expression of the renin-angiotensin system in human podocytes | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1152/ajprenal.00475.2004 | - |
dc.identifier.scopus | eid_2-s2.0-33645577151 | - |
dc.identifier.volume | 290 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | F710 | - |
dc.identifier.epage | F719 | - |
dc.identifier.isi | WOS:000235082700019 | - |
dc.identifier.issnl | 0363-6127 | - |