Hayata Nozomi, Fujio Yasushi, Yamamoto Yasuhiro, Iwakura Tomohiko, Obana Masanori, Takai Mika, Mohri Tomomi, Nonen Shinpei, Maeda Makiko, Azuma Junichi
Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2008 May 30;370(2):274-8. doi: 10.1016/j.bbrc.2008.03.100. Epub 2008 Mar 28.
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.
在心脏重塑过程中，心肌细胞会分泌结缔组织生长因子（CTGF/CCN2）。尽管已知CTGF可促进成纤维细胞增殖，但其在心肌细胞中的病理生理作用仍有待阐明。在本研究中，我们检测了CTGF对大鼠新生心肌细胞的生物学效应。用全长CTGF及其C末端区域肽刺激的心肌细胞显示细胞表面积增加。与G蛋白偶联受体的肥大性配体（如内皮素-1）类似，CTGF激活了氨基酸摄取；然而，通过Northern印迹分析，CTGF诱导的肥大与骨骼肌动蛋白或脑钠肽（BNP）表达增加无关。CTGF处理激活了ERK1/2、p38 MAPK、JNK和Akt。通过转导显性负性Akt抑制Akt可消除CTGF介导的细胞大小增加，而抑制MAP激酶并不影响心肌肥大。这些发现表明CTGF是心肌细胞中的一种新型肥大因子。
