title: Paracrine actions of cardiac fibroblasts on cardiomyocytes: implications for the cardiac renin-angiotensin system.
abstract: Conditioned medium of cardiac fibroblasts was found to induce protein synthesis and signal transduction events rapidly, and to increase angiotensinogen messenger RNA (mRNA) levels in neonatal rat ventricular myocytes. Within 4 hours, fibroblast-conditioned medium (FCM) stimulated protein synthesis in cardiac myocytes, independent of the contractile state, and induced marked increases within 24 hours in total protein content. Endothelin- released by cardiac fibroblasts was not responsible for the stimulation of protein synthesis. FCM rapidly activated signal transduction events in cardiac myocytes associated with hypertrophic stimuli, including: (1) increased tyrosine phosphorylation of several prominent protein bands; (2) mitogen-activated protein kinases (ERK 1 and ERK 2); and (3) protein kinase C. Finally, FCM caused an increase at 8 hours in angiotensinogen mRNA levels of cardiac myocytes, whereas no effect was observed on mRNA levels for renin or the type 1 angiotensin II receptor (AT1). Our results suggest that cardiac fibroblasts produce a factor that rapidly activates cardiac myocyte growth through a membrane receptor that couples to conventional signal transduction pathways.
authors.affiliation: The Pennsylvania State University College of Medicine, Weis Center for Research, Danville, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Booz
authors.forename: D E
authors.initials: DE
authors.lastname: Dostal
authors.forename: K M
authors.initials: KM
authors.lastname: Baker
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D019332:Endothelin-1 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006321:Heart / Q000254:growth & development; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D019332:Endothelin-1; D012333:RNA, Messenger; D000808:Angiotensinogen; D010770:Phosphotransferases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases