Volume 11 Supplement 1

5th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access

Suppression of kidney fibrosis by cGMP-dependent protein kinase I

  • Elisabeth Schinner1Email author,
  • Armin Kurtz2,
  • Franz Hofmann3 and
  • Jens Schlossmann1
BMC Pharmacology201111(Suppl 1):P62

https://doi.org/10.1186/1471-2210-11-S1-P62

Published: 1 August 2011

Background

cGMP is synthesized via nitric oxide- or natriuretic peptide-stimulated guanylyl cyclases and exhibits pleiotropic regulatory functions also in the kidney. Hence, the integration of cGMP signaling via cGMP-dependent protein kinases (cGK) might play a critical role for renal physiology. Both isozymes were detected in arterioles, mesangium and within the cortical interstitium. In contrast to cGKIα, the β isoform was not detected in the juxtaglomerular apparatus and medullary fibroblasts.

Results

Here, we examined the function of cGKI in the renal interstitium emphasizing a functional differentiation of both isoforms. The interstitium exists mainly of fibroblasts playing a prominent role in the interstitial fibrosis. Accordingly, cGKI could also be involved in this pathophysiological process. Therefore, we studied whether cGKI influences renal fibrosis by application of cGMP increasing YC-1 or ISDN and by using mutant mice. The kidney-fibrosis was induced by unilateral ureter obstruction (UUO).

Conclusion

Administration of ISDN showed significantly antifibrotic effects in wt- but not in αSM-rescue mice. Also tg-tg mice which express more cGKIα developed significantly less fibrosis than wt mice. Moreover, mRNA- and protein expression of cGKIβ was fewer influenced by fibrosis than cGKIα. Accordingly, our results indicate that cGMP acts primarily via cGKIα as an important suppressor of kidney fibrosis.

Authors’ Affiliations

(1)
Pharmakologie und Toxikologie, Universität Regensburg
(2)
Physiologie, Universität Regensburg
(3)
Carvas-Zentrum, TU München

Copyright

© Schinner et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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