Interactions between cardiac cells enhance cardiomyocyte hypertrophy and increase fibroblast proliferation
Interactions between cardiac cells enhance cardiomyocyte hypertrophy and increase fibroblast proliferation
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DOI：
10.1002/jcp.20197
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发表时间：
2005-03-01
影响因子：
5.6
通讯作者：
Potreau, D
中科院分区：
文献类型：
--
作者：
Fredj, S;Bescond, J;Potreau, D
在心肌肥大中，心肌细胞（CM）的过度增大和进行性纤维化是同时发生的。为了研究在这些条件下心室CM和心脏成纤维细胞（CF）之间相互作用的性质，我们建立了一个成年小鼠CM与CF共培养的“去分化模型”。在这样一个模型中，这是公认的研究心脏细胞肥大在体外，去分化的CM在文化和共培养的特点是免疫阳性染色的心钠素（心房利钠肽）和β-肌球蛋白重链（β-MHC）。结果证实，在培养期间，CM分泌ANP显著增加。在CM/CF共培养中培养的CM的增加尺寸显著高于CM培养物，当CM与成纤维细胞条件培养基（FCM）一起培养时也观察到这一点。此外，成纤维细胞增殖研究表明，CM有利于成纤维细胞粘附和/或生长在共培养的开始和成纤维细胞增殖的整个时间过程中的共培养。此外，在CM/CF共培养物中通过ELISA检测到显著水平的白细胞介素-6（IL-6）产生。当在FCM存在下培养CM时，观察到类似的更高的增加。这些结果表明，CF增强肌细胞肥大和CM调节成纤维细胞粘附和/或增殖，表明CM和CF之间的旁分泌相互作用，这可能涉及IL-6。(C)2004威利-利斯公司
In cardiac hypertrophy, both excessive enlargement of cardiac myocytes (CMs) and progressive fibrosis are known to occur simultaneously. To investigate the nature of interactions between ventricular CMs and cardiac fibroblasts (CFs) in these conditions, we have established a "dedifferentiated model" of adult murine CMs in coculture with CFs. In such a model, which is recognized to study cardiac cell hypertrophy in vitro, dedifferentiated CMs in Culture and in coculture were characterized by immunopositive staining to ANP (atrial natriuretic peptide) and beta-myosin heavy chain (beta-MHC). The results confirm that ANP secretion by CMs was significantly increased during the Cultures. The increase size of cultured CMs was significantly higher in CM/CF cocultures than in CM Cultures which was also observed when CMs were Cultured with fibroblast conditioned medium (FCM). In addition, fibroblast proliferation studies showed that CMs favored fibroblast adhesion and/or growth at the beginning of the coculture and fibroblast proliferation throughout the time course of the coculture. Furthermore, a significant level of interleukin-6 (IL-6) production was detected by ELISA in CM/CF cocultures. A similar higher increase was observed when CMs were cultured in the presence of FCM. These results demonstrate that CFs enhance myocyte hypertrophy and that CMs regulate fibroblast adhesion and/or proliferation, suggesting a paracrine interaction between CMs and CFs which could involve IL-6. (C) 2004 Wiley-Liss, Inc.