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

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Title: Quantitative analysis of the cardiac fibroblast transcriptome-implications for NO/cGMP signaling
Authors: Smolenski, Albert P.
Schultess, Jan
Danielewski, Oliver
et al.
Permanent link: http://hdl.handle.net/10197/6006
Date: Apr-2004
Online since: 2014-10-06T11:28:15Z
Abstract: 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.
Type of material: Journal Article
Publisher: Elsevier
Journal: Genomics
Volume: 83
Issue: 4
Start page: 577
End page: 587
Copyright (published version): 2003 Elsevier
Keywords: Cardiac fibroblastSAGEGene expressioncGMPProtein kinaseProliferation
DOI: 10.1016/j.ygeno.2003.10.002
Language: en
Status of Item: Peer reviewed
Appears in Collections:Medicine Research Collection

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