Quantitative analysis of the cardiac fibroblast transcriptome implications for NO/cGMP signaling

  • Cardiac fibroblasts regulate tissue repair and remodeling in the heart. To quantify transcript levels in these cells we performed a comprehensive gene expression study using serial analysis of gene expression (SAGE). Among 110,169 sequenced tags we could identify 30,507 unique transcripts. A comparison of SAGE data from cardiac fibroblasts with data derived from total mouse heart revealed a number of fibroblast-specific genes. Cardiac fibroblasts expressed a specific collection of collagens, matrix proteins and metalloproteinases, growth factors, and components of signaling pathways. The NO/cGMP signaling pathway was represented by the mRNAs for α1 and β1 subunits of guanylyl cyclase, cGMP-dependent protein kinase type I (cGK I), and, interestingly, the G-kinase-anchoring protein GKAP42. The expression of cGK I was verified by RT-PCR and Western blot. To establish a functional role for cGK I in cardiac fibroblasts we studied its effect on cell proliferation. Selective activation of cGK I with a cGMP analog inhibited the proliferation of serum-stimulated cardiac fibroblasts, which express cGK I, but not higher passage fibroblasts, which contain no detectable cGK I. Currently, our data suggest that cGK I mediates the inhibitory effects of the NO/cGMP pathway on cardiac fibroblast growth. Furthermore the SAGE library of transcripts expressed in cardiac fibroblasts provides a basis for future investigations into the pathological regulatory mechanisms underlying cardiac fibrosis.

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Author:Albert Smolenski, Jan Schultess, Oliver Danielewski, Maisa I. Garcia Arguinzonis, Petra Thalheimer, Susanne Kneitz, Ulrich Walter, Suzanne M. Lohmann
URN:urn:nbn:de:hebis:30:3-344221
Handle:http://hdl.handle.net/10197/6006
DOI:https://doi.org/10.1016/j.ygeno.2003.10.002
ISSN:1089-8646
ISSN:0888-7543
Parent Title (English):Genomics
Publisher:Academic Press
Place of publication:San Diego, Calif.
Document Type:Article
Language:English
Date of Publication (online):2014/11/25
Year of first Publication:2004
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/11/25
Tag:Cardiac fibroblast; Gene expression; Proliferation; Protein kinase; SAGE; cGMP
Volume:83
Issue:4
Page Number:29
First Page:577
Last Page:587
Note:
This is the author’s version of a work that was accepted for publication in Genomics . Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Genomics (VOL 83, ISSUE 4, (2004)) DOI: 10.1016/j.ygeno.2003.10.002
Note:
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.
HeBIS-PPN:353832308
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0