Smolenski, Albert P.Albert P.SmolenskiSchultess, JanJanSchultessDanielewski, OliverOliverDanielewskiet al.2014-10-062014-10-062003 Elsev2004-04Genomicshttp://hdl.handle.net/10197/6006Cardiac 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.enThis 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.2003.10.002Cardiac fibroblastSAGEGene expressioncGMPProtein kinaseProliferationJournal Article83457758710.1016/j.ygeno.2003.10.0022014-08-13https://creativecommons.org/licenses/by-nc-nd/3.0/ie/