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首页> 外文期刊>Molecular biology of the cell >CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin
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CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin

机译：CCN2（结缔组织生长因子）促进成纤维细胞与纤连蛋白的粘附

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摘要

In vivo, CCN2 (connective tissue growth factor) promotes angiogenesis, osteogenesis, tissue repair, and fibrosis, through largely unknown mechanisms. In vitro, CCN2 promotes cell adhesion in a variety of systems via integrins and heparin sulfate proteoglycans (HSPGs). However, the physiological relevance of CCN2-mediated cell adhesion is unknown. Here, we find that HSPGs and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade are required for adult human dermal fibroblasts to adhere to CCN2. Endogenous CCN2 directly binds fibronectin and the fibronectin receptors integrins alpha4 beta1 and alpha5 and syndecan 4. Using Ccn2-/- mouse embryonic fibroblasts, we show that loss of endogenous CCN2 results in impaired spreading on fibronectin, delayed a-smooth muscle actin stress fiber formation, and reduced ERK and focal adhesion kinase phosphorylation. These results suggest that a physiological role of CCN2 is to potentiate the ability of fibroblasts to spread on fibronectin, which may be important in modulating fibroblast adhesion to the provisional matrix during tissue development and wound healing. These results are consistent with the notion that a principal function of CCN2 is to modulate receptor/ligand interactions in vivo.
机译：在体内，CCN2（结缔组织生长因子）通过很大程度上未知的机制促进血管生成，成骨，组织修复和纤维化。在体外，CCN2通过整联蛋白和硫酸肝素蛋白聚糖（HSPG）促进多种系统中的细胞粘附。但是，尚不清楚CCN2介导的细胞粘附的生理相关性。在这里，我们发现，成年人类真皮成纤维细胞要粘附到CCN2，就需要HSPGs和促分裂原激活的蛋白激酶激酶/细胞外信号调节激酶（ERK）促分裂原激活的蛋白激酶级联反应。内源性CCN2直接结合纤连蛋白和纤连蛋白受体整合素alpha4 beta1和alpha5和syndecan4。使用Ccn2-/-小鼠胚胎成纤维细胞，我们显示内源性CCN2的丧失导致纤连蛋白的扩散受损，延迟了a-平滑肌肌动蛋白应力纤维的形成。 ，并减少ERK和粘着斑激酶磷酸化。这些结果表明，CCN2的生理作用是增强成纤维细胞在纤连蛋白上扩散的能力，这可能在组织发育和伤口愈合过程中调节成纤维细胞对临时基质的粘附中很重要。这些结果与CCN2的主要功能是调节体内受体/配体相互作用的观点一致。

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