Connective tissue growth factor induces cardiac hypertrophy through Akt signaling

• Published in: Biochemical and biophysical research communications Vol. 370; no. 2; pp. 274 - 278
• Main Authors: Hayata, Nozomi, Fujio, Yasushi, Yamamoto, Yasuhiro, Iwakura, Tomohiko, Obana, Masanori, Takai, Mika, Mohri, Tomomi, Nonen, Shinpei, Maeda, Makiko, Azuma, Junichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.05.2008
• Subjects: 60 APPLIED LIFE SCIENCES; ACTIN; Akt; AMINO ACIDS; Amino Acids - metabolism; Animals; BIOLOGICAL EFFECTS; Cardiac myocyte; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomegaly - pathology; CCN family; Cell Size - drug effects; Cells, Cultured; CONNECTIVE TISSUE; Connective Tissue Growth Factor; FIBROBLASTS; Gene Expression - drug effects; GROWTH FACTORS; GTP-ASES; HYPERTROPHY; Immediate-Early Proteins - genetics; Immediate-Early Proteins - pharmacology; Immediate-Early Proteins - physiology; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - pharmacology; Intercellular Signaling Peptides and Proteins - physiology; LIGANDS; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; PEPTIDES; PHOSPHOTRANSFERASES; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; RATS; RECEPTORS; Recombinant Proteins - genetics; Recombinant Proteins - pharmacology; Signal Transduction; Connective tissue growth factor; CCN family; Cardiac myocyte; Akt; Hypertrophy
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.03.100

In the process of cardiac remodeling, connective tissue growth factor (CTGF/CCN2) is secreted from cardiac myocytes. Though CTGF is well known to promote fibroblast proliferation, its pathophysiological effects in cardiac myocytes remain to be elucidated. In this study, we examined the biological effects of CTGF in rat neonatal cardiomyocytes. Cardiac myocytes stimulated with full length CTGF and its C-terminal region peptide showed the increase in cell surface area. Similar to hypertrophic ligands for G-protein coupled receptors, such as endothelin-1, CTGF activated amino acid uptake; however, CTGF-induced hypertrophy is not associated with the increased expression of skeletal actin or BNP, analyzed by Northern-blotting. CTGF treatment activated ERK1/2, p38 MAPK, JNK and Akt. The inhibition of Akt by transducing dominant-negative Akt abrogated CTGF-mediated increase in cell size, while the inhibition of MAP kinases did not affect the cardiac hypertrophy. These findings indicate that CTGF is a novel hypertrophic factor in cardiac myocytes.