Antifibrotic effects of CCN1/CYR61 in primary portal myofibroblasts through induction of reactive oxygen species and resulting apoptosis

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

“…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 transdifferentiation into fully differentiated myofibroblasts representing the key cellular subtype contributing to the progression of hepatic fibrogenesis.…”

“…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 transdifferentiation 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).…”