Ccn1, a molecular switch that imposes a self-limiting control on inflammation and wound healing in a multitude of organs?

摘要

to the editor: With great interest I have read the paper of Grazioli and colleagues that appeared in one of the April issues of this year (5). The findings that CCN1 expression increases in murine lung after bleomycin instillation and that the adenoviral transfer of CCN1 induces acute lung injury are of course very exciting. These observations strongly support our own experimental findings showing an increase in CCN1 expression during acute liver injury (2). In this former study, we have also found that the expression of CCN1 is strongly upregulated in activated hepatic stellate cells, whereas the expression decreases time dependently in these cells during transdifferentia-tion into fully differentiated myofibroblasts representing the key cellular subtype contributing to the progression of hepatic fibrogenesis. Moreover, we demonstrated that the adenoviral overexpression of CCN1 in mice induces production of reactive oxygen species leading to dose-dependent cellular senescence and apoptosis of liver cells (2). At that time our study was mainly inspired by the pioneering work of Lester F. Lau, who has established for the first time that CCN1 is a key player with a property to induce fibroblast senescence and restrict fibrosis in cutaneous wound healing (6). Moreover, Lau proved the ability of this matrix cell-adhesion molecule to trigger the formation and accumulation of a robust and sustained level of reactive oxygen species (7). So all these data obtained in skin, in liver, and now in lung might unanimously predict that CCN1 is a molecular switch that imposes a self-limiting control on inflammation and wound healing in a variety or potentially all organs.