Connective tissue growth factor induces cardiac hypertrophy through Akt signaling
Connective tissue growth factor induces cardiac hypertrophy through Akt signaling
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DOI：
10.1016/j.bbrc.2008.03.100
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发表时间：
2008-05-30
影响因子：
3.1
通讯作者：
Azuma, Junichi
中科院分区：
文献类型：
--
作者：
Hayata, Nozomi;Fujio, Yasushi;Azuma, Junichi
在心脏重构过程中，心肌细胞分泌结缔组织生长因子(CTGF/CCN2)。虽然CTGF促进成纤维细胞增殖是众所周知的，但其在心肌细胞中的病理生理作用仍不清楚。在本研究中，我们检测了CTGF对新生大鼠心肌细胞的生物学效应。心肌细胞经全长CTGF及其C末端多肽刺激后，细胞表面积明显增加。与G蛋白偶联受体的肥大配体类似，CTGF激活氨基酸摄取；然而，Northern-blotting分析，CTGF诱导的肥大与骨骼肌动蛋白或BNP表达的增加无关。CTGF可激活ERK1/2、p38MAPK、JNK和Akt。通过转导显性-负性Akt来抑制Akt可阻断CTGF介导的细胞增大，而抑制MAP激酶不影响心肌肥大。这些结果表明CTGF是一种新的心肌细胞肥大因子。(C)2008 Elsevier Inc.保留所有权利。
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. (C) 2008 Elsevier Inc. All rights reserved.