J Cell Commun Signal. 2010 Mar;4(1):1-4. doi: 10.1007/s12079-009-0071-5. Epub 2009 Oct 2.
In recent months, four different systems have been reported in the literature in which CCN2 transgenes were individually expressed in podocytes, hepatocytes, cardiomyocytes or respiratory epithelial cells to achieve overexpression in, respectively, the kidney, liver, heart, or lung. These transgenic systems have provided valuable information about the contribution of CCN2 to fibrosis in vivo and have begun to reveal the complexities of the underlying mechanisms involved. On the one hand, studies of these animals have revealed that CCN2 overexpression does not necessarily lead directly to fibrotic pathology but may cause severe non-fibrotic tissue damage due to its other effects on cell function (e.g. heart). On the other hand, overexpression of CCN2 in concert with signaling pathways associated with development (e.g. lung) or fibrosing injuries (e.g. kidney, liver) can lead to the initiation or exacerbation of fibrosis. The significance of these studies is discussed in the context of the requirement for interactions between CCN2 and co-stimulatory factors in the microenvironment for the manifestation of CCN2-dependent fibrosis.
最近几个月，文献中报道了四种不同的系统，其中 CCN2 转基因分别在足细胞、肝细胞、心肌细胞或呼吸上皮细胞中表达，分别在肾脏、肝脏、心脏或肺部实现过表达。这些转基因系统为 CCN2 在体内纤维化中的作用提供了有价值的信息，并开始揭示涉及的潜在机制的复杂性。一方面，这些动物的研究表明，CCN2 的过表达不一定直接导致纤维化病理，但由于其对细胞功能的其他影响（例如心脏），可能导致严重的非纤维性组织损伤。另一方面，CCN2 的过表达与与发育（例如肺）或纤维化损伤（例如肾、肝）相关的信号通路一起，可能导致纤维化的起始或加剧。这些研究的意义是在微环境中 CCN2 与协同刺激因子相互作用以表现出 CCN2 依赖性纤维化的要求的背景下讨论的。
