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Report on the Third International Workshop on the CCN Family of Genes
The CCN family currently comprises six extracellular matrix associated proteins (CCN1–6) that regulate diverse cell functions. Although CCN molecules regulate vital processes in vivo (for example, chondrogenesis, angiogenesis, and matrix remodelling) and are associated with several pathophysiological disorders (such as fibrosis and tumorigenesis), it has been a challenge to define the underlying biological mechanisms involved. Progress has been hampered by the disparate in vivo and in vitro models used by investigators in the field, and by the difficulty in obtaining validated reagents (particularly recombinant CCN proteins) for experimental use. In spite of these drawbacks, there have been many exciting developments in the field over the past few years, and it was against this backdrop that investigators convened for the Third International Workshop on the CCN Family of Genes in St Malo, France on 20–23 October 2004.
GENE EXPRESSION
Although studies in the early 1990s showed that CCN1 and CCN2 were encoded by immediate early genes, current research in the field highlights the diverse mechanisms that influence the regulation of CCN gene expression. M Goppelt-Struebe (Germany) reported that CCN2 expression in endothelial cells or fibroblasts is inhibited by monomeric G actin, but it is stimulated by F actin stress fibres, emphasising the importance of changes in cell morphology as a determinant of CCN2 production. R O’Leary (Ireland) reported the downregulation and disassembly of several cytoskeletal proteins in human glomerular mesangial cells in response to CCN2, suggesting that actin reorganisation is among the pathophysiological effects of CCN2 in diabetic nephropathy.
CCN2 is a well characterised regulator of chondrogenesis and S Kubota (Japan) reported that CCN2 expression was enhanced during chick chondrocyte differentiation as a result of enhanced gene transcription and mRNA stabilisation, the latter of which was attributed to a novel regulatory element …