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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
ROLE OF CGMP-DEPENDENT PROTEIN KINASE I FOR RENAL FIBROSIS
Abstract number: P236
Schinner
1
*E.
, Schramm
1
A., Hofmann
2
F., Schlossmann
1
J.
1
University of Regensburg, Pharmacology and Toxicology, Regensburg, Germany
2
University of Munich, Pharmacology and Toxicology, Munich, Germany
cGMP is synthesized via nitric oxide- or natriuretic peptide-stimulated guanylyl cyclases and exhibits pleiotropic regulatory functions in kidney. The two isoforms of the cGMP-dependent protein kinases cGKIα and cGKIβ can be activated by cGMP.
Here, we focused on the function of cGKI in interstitial fibrosis. Interstitial fibroblasts play a prominent role in renal fibrosis. In cortical interstitium, we detected both isoforms but in medullary interstitium, we only could find cGKIα. Therefore, we studied whether cGKI influences renal fibrosis induced by unilateral ureter obstruction (UUO). After administration of a cGMP-increasing agent (YC1), we could detect stronger antifibrotic effects regarding mRNA- and protein expression of different fibrosis marker (TGFβ, Col1a1, fibronectin) in wt mice than in cGKI-KO-mice or in SM-cGKIα-rescue mice (cGKI deficient in kidney with exception of renal vasculature).
Our results indicate that cGMP acts via cGKI as an important suppressor of kidney fibrosis.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P236