Quantitative analysis of the cardiac fibroblast transcriptome-implications for NO/cGMP signaling
|Title:||Quantitative analysis of the cardiac fibroblast transcriptome-implications for NO/cGMP signaling||Authors:||Smolenski, Albert P.
|Permanent link:||http://hdl.handle.net/10197/6006||Date:||Apr-2004||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||Copyright (published version):||2003 Elsevier||Keywords:||Cardiac fibroblast;SAGE;Gene expression;cGMP;Protein kinase;Proliferation||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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