Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.
J Cell Commun Signal. 2013 Mar;7(1):11-8. doi: 10.1007/s12079-012-0180-4. Epub 2012 Oct 14.
CCN family proteins 2 and 3 (CCN2 and CCN3) belong to the CCN family of proteins, all having a high level of structural similarity. It is widely known that CCN2 is a profibrotic molecule that mediates the development of fibrotic disorders in many different tissues and organs. In contrast, CCN3 has been recently suggested to act as an anti-fibrotic factor in several tissues. This CCN3 action was shown earlier to be exerted by the repression of the CCN2 gene expression in kidney tissue, whereas different findings were obtained for liver cells. Thus, the molecular action of CCN3 yielding its anti-fibrotic effect is still controversial. Here, using a general model of fibrosis, we evaluated the effect of CCN3 overexpression on the gene expression of all of the CCN family members, as well as on that of fibrotic marker genes. As a result, repression of CCN2 gene expression was modest, while type I collagen and α-smooth muscle actin gene expression was prominently repressed. Interestingly, not only CCN2, but also CCN4 gene expression showed a decrease upon CCN3 overexpression. These findings indicate that fibrotic gene induction is under the control of a complex molecular network conducted by CCN family members functioning together.
CCN 家族蛋白 2 和 3（CCN2 和 CCN3）属于 CCN 家族蛋白，它们都具有高度的结构相似性。众所周知，CCN2 是一种促纤维化分子，可介导多种不同组织和器官中纤维化疾病的发展。相比之下，CCN3 最近被认为在几种组织中是一种抗纤维化因子。这种 CCN3 作用先前被证明是通过抑制肾脏组织中 CCN2 基因的表达来发挥的，而在肝细胞中则得到了不同的发现。因此，CCN3 产生其抗纤维化作用的分子作用仍存在争议。在这里，我们使用纤维化的一般模型，评估了 CCN3 过表达对所有 CCN 家族成员以及纤维化标记基因的基因表达的影响。结果表明，CCN2 基因表达的抑制作用适中，而 I 型胶原和α-平滑肌肌动蛋白基因表达则明显受到抑制。有趣的是，CCN3 过表达不仅会降低 CCN2 基因的表达，还会降低 CCN4 基因的表达。这些发现表明，纤维化基因的诱导受到由 CCN 家族成员共同作用的复杂分子网络的控制。
