Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling.
Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling.
复制标题
心脏成纤维细胞通过Beta1整合素信号传导调节心肌增殖。
DOI：
10.1016/j.devcel.2008.12.007
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发表时间：
2009-02
影响因子：
11.8
通讯作者：
Srivastava, Deepak
中科院分区：
文献类型：
--
作者：
Leda, Masaki;Tsuchihashi, Takatoshi;Ivey, Kathryn N.;Ross, Robert S.;Hong, Ting-Ting;Shaw, Robin M.;Srivastava, Deepak
心室腔的生长和扩张在心脏发育过程中是必不可少的，并通过心脏祖细胞的增殖来实现。相比之下，成年心肌细胞通过肥大而不是增生来实现生长。虽然心外膜来源的信号可能有助于心肌细胞的增殖过程，但导致心室心肌厚度发展的因素和细胞类型尚不清楚。使用共培养系统，我们发现，胚胎心脏成纤维细胞诱导心肌细胞增殖，与成人心脏成纤维细胞，促进心肌细胞肥大。我们确定了纤维连接蛋白，胶原蛋白和肝素结合EGF样生长因子作为胚胎心脏成纤维细胞特异性信号，协同促进心肌细胞增殖的旁分泌方式。这种增殖反应需要β1-整合素，小鼠心室心肌细胞特异性缺失β1-整合素导致心肌增殖减少和心室致密化受损。这些发现揭示了一个以前未被认识的旁分泌功能的胚胎心脏成纤维细胞在调节心肌细胞增殖。
Growth and expansion of ventricular chambers is essential during heart development and is achieved by proliferation of cardiac progenitors. Adult cardiomyocytes, by contrast, achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Using a co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. β1-integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of β1-integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation.
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影响因子：
64.8
作者：
Laugwitz, KL;Moretti, A;Chien, KR
通讯作者：
Chien, KR
影响因子：
82.9
作者：
Ieda, Masaki;Kanazawa, Hideaki;Fukuda, Keiichi
通讯作者：
Fukuda, Keiichi
DOI：
10.1073/pnas.0802319105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Peng, Xu;Wu, Xiaoyang;Guan, Jun-Lin
通讯作者：
Guan, Jun-Lin
影响因子：
11.8
作者：
Grego-Bessa, Joaquin;Luna-Zurita, Luis;de la Pompa, Jose Luis
通讯作者：
de la Pompa, Jose Luis
影响因子：
64.8
作者：
Cai, Chen-Leng;Martin, Jody C.;Evans, Sylvia M.
通讯作者：
Evans, Sylvia M.