Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy.
Fibronectin (FN) is an extracellular matrix protein that binds to integrin receptors and couples cardiac myocytes to the basal lamina. Cardiac FN expression is elevated in models of pressure overload, and FN causes cultured cardiac myocytes to hypertrophy by a mechanism that has not been characterized in detail. In this study, we analyzed the gene expression changes induced by FN in purified rat neonatal ventricular myocytes using the Affymetrix RAE230A microarray, to understand how FN affects gene expression in cardiac myocytes and to separate the effects contributed by cardiac nonmyocytes in vivo. Pathway analysis using z-score statistics and comparison with a mouse model of cardiac hypertrophy revealed several pathways stimulated by FN in cardiac myocytes. In addition to the known cardiac myocyte hypertrophy markers, FN significantly induced metabolic pathways including virtually all of the enzymes of cholesterol biosynthesis, fatty acid biosynthesis, and the mitochondrial electron transport chain. FN also increased the expression of genes coding for ribosomal proteins, translation factors, and the ubiquitin-proteasome pathway. Interestingly, cardiac myocytes plated on FN showed elevated expression of the fibrosis-promoting peptides connective tissue growth factor (CTGF), WNT1 inducible signaling pathway protein 2 (WISP2), and secreted acidic cysteine-rich glycoprotein (SPARC). Our data complement in vivo studies and reveal several novel genes and pathways stimulated by FN, pointing to cardiac myocyte-specific mechanisms that lead to development of the hypertrophic phenotype.
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Hua
H
Chen
Xueyin N
XN
Huang
Alexandre F R
AF
Stewart
Jorge L
JL
Sepulveda
D000818:Animals; D000831:Animals, Newborn; D001018:Aortic Diseases / Q000235:genetics; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004579:Electron Transport / Q000235:genetics; D005353:Fibronectins / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics*; D005796:Genes / Q000235:genetics; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy / Q000139:chemically induced* / Q000235:genetics*; D051379:Mice; D032383:Myocytes, Cardiac / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D003598:Cytoskeletal Proteins; D005353:Fibronectins