Connective tissue growth factor overexpression in cardiomyocytes promotes cardiac hypertrophy and protection against pressure overload.
Connective tissue growth factor overexpression in cardiomyocytes promotes cardiac hypertrophy and protection against pressure overload.
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DOI：
10.1371/journal.pone.0006743
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发表时间：
2009-08-25
期刊：
影响因子：
3.7
通讯作者：
Ozcelik C
中科院分区：
文献类型：
--
作者：
Panek AN;Posch MG;Alenina N;Ghadge SK;Erdmann B;Popova E;Perrot A;Geier C;Dietz R;Morano I;Bader M;Ozcelik C
结缔组织生长因子（CTGF）是一种分泌性蛋白质，在人类和实验性心力衰竭中强烈诱导。CTGF被认为是促纤维化的;然而，CTGF的确切功能尚不清楚。我们产生了转基因小鼠和大鼠心肌细胞特异性CTGF过表达（CTGF-TG）。为了研究CTGF作为纤维化诱导剂，我们进行了CTGF-TG小鼠和大鼠心脏的基础条件下，血管紧张素II（Ang II）或异丙肾上腺素刺激后的形态和基因表达分析。令人惊讶的是，两种模型的心脏组织均未显示纤维化增加或纤维化标志物的基因表达增强。与对照组相比，血管紧张素II治疗的CTGF-TG小鼠显示出保留的心脏功能。然而，CTGF-TG小鼠在7个月大时出现年龄依赖性心功能障碍。CTGF相关的心力衰竭与Akt和JNK激活有关，但与利钠肽的诱导无关。此外，CTGF-TG小鼠的心肌细胞显示出不受影响的细胞收缩性和增加的肌浆网Ca 2+再摄取。在缺血/再灌注模型中，CTGF-TG心脏与对照组没有差异。我们的数据表明，CTGF本身并不诱导心脏纤维化。此外，它还参与心肌肥大诱导和细胞重塑，这取决于心脏应激刺激。我们新的转基因动物是重新考虑CTGF在心脏中的促纤维化功能的有价值的模型。
Connective tissue growth factor (CTGF) is a secreted protein that is strongly induced in human and experimental heart failure. CTGF is said to be profibrotic; however, the precise function of CTGF is unclear. We generated transgenic mice and rats with cardiomyocyte-specific CTGF overexpression (CTGF-TG). To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat hearts under basal conditions and after stimulation with angiotensin II (Ang II) or isoproterenol, respectively. Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. In contrast to controls, Ang II treated CTGF-TG mice displayed preserved cardiac function. However, CTGF-TG mice developed age-dependent cardiac dysfunction at the age of 7 months. CTGF related heart failure was associated with Akt and JNK activation, but not with the induction of natriuretic peptides. Furthermore, cardiomyocytes from CTGF-TG mice showed unaffected cellular contractility and an increased Ca2+ reuptake from sarcoplasmatic reticulum. In an ischemia/reperfusion model CTGF-TG hearts did not differ from controls. Our data suggest that CTGF itself does not induce cardiac fibrosis. Moreover, it is involved in hypertrophy induction and cellular remodeling depending on the cardiac stress stimulus. Our new transgenic animals are valuable models for reconsideration of CTGF's profibrotic function in the heart.
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影响因子：
5
作者：
Gabrielsen, Anders;Lawler, Patrick R.;Hansson, Goran K.
通讯作者：
Hansson, Goran K.
DOI：
10.1016/j.bbrc.2008.03.100
发表时间：
2008-05-30
影响因子：
3.1
作者：
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通讯作者：
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158.5
作者：
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通讯作者：
Vasan, RS
影响因子：
13.6
作者：
Riser, BL;Denichilo, M;Narins, RG
通讯作者：
Narins, RG
影响因子：
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作者：
Chien, KR
通讯作者：
Chien, KR