Paracrine actions of cardiac fibroblasts on cardiomyocytes: implications for the cardiac renin-angiotensin system.
Paracrine actions of cardiac fibroblasts on cardiomyocytes: implications for the cardiac renin-angiotensin system.
复制标题
心脏成纤维细胞对心肌细胞的旁分泌作用：对心脏肾素-血管紧张素系统的影响。
DOI：
10.1016/s0002-9149(99)00257-x
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Baker,KM
中科院分区：
文献类型：
--
作者：
Booz,GW;Dostal,DE;Baker,KM
心脏成纤维细胞条件培养液能迅速诱导新生大鼠心室肌细胞蛋白质合成和信号转导，并增加血管紧张素原信使RNA（mRNA）水平。在4小时内，成纤维细胞条件培养基（FCM）刺激心肌细胞的蛋白质合成，独立的收缩状态，并诱导显着增加在24小时内的总蛋白含量。心脏成纤维细胞释放的内皮素-1对蛋白质合成的刺激不起作用。FCM快速激活与肥大刺激相关的心肌细胞中的信号转导事件，包括：（1）几个显著蛋白条带的酪氨酸磷酸化增加;（2）丝裂原活化蛋白激酶（ERK 1和ERK 2）;和（3）蛋白激酶C。最后，FCM引起心肌细胞血管紧张素原mRNA水平在8小时的增加，而没有观察到对肾素或1型血管紧张素II受体（AT 1）的mRNA水平的影响。我们的研究结果表明，心脏成纤维细胞产生的因子，通过膜受体，耦合到传统的信号转导途径，迅速激活心肌细胞的生长。
Conditioned medium of cardiac fibroblasts was found to induce protein synthesis and signal transduction events rapidly, and to increase angiotensinogen messenger RNA (mRNA) levels in neonatal rat ventricular myocytes. Within 4 hours, fibroblast-conditioned medium (FCM) stimulated protein synthesis in cardiac myocytes, independent of the contractile state, and induced marked increases within 24 hours in total protein content. Endothelin-1 released by cardiac fibroblasts was not responsible for the stimulation of protein synthesis. FCM rapidly activated signal transduction events in cardiac myocytes associated with hypertrophic stimuli, including: (1) increased tyrosine phosphorylation of several prominent protein bands; (2) mitogen-activated protein kinases (ERK 1 and ERK 2); and (3) protein kinase C. Finally, FCM caused an increase at 8 hours in angiotensinogen mRNA levels of cardiac myocytes, whereas no effect was observed on mRNA levels for renin or the type 1 angiotensin II receptor (AT1). Our results suggest that cardiac fibroblasts produce a factor that rapidly activates cardiac myocyte growth through a membrane receptor that couples to conventional signal transduction pathways.