Does LOXL2 and JNK MAP kinase activation mediate CCN2CTGF-induced collagen accumulation in gingival fibroblasts?

Abstract

CCN2/CTGF is a member of the CCN family of matricellular proteins, functioning in collaboration with other factors and extracellular matrix components. CCN proteins bind receptors including low-density lipoprotein related proteins and integrins (Heng et al., 2006). Even after all that has been discovered about CCN2/CTGF over the last two decades, not everything is known today, for example the mechanism by which CCN2/CTGF stimulates collagen deposition (Crean et al., 2002). Gingival fibrosis is defined by accumulation of excess gingival tissue and is characterized by excess extracellular matrix accumulation and elevated levels of cytokines in the absence of periodontal bone loss. Drug-induced gingival fibrosis is the adverse effect of three types of medications: 1) calcium channel blockers, 2) immunosuppressive cyclosporine A, and 3) antiseizure drugs. After culturing gingival fibroblasts (GFs), evidence revealed notable levels of CCN2/CTGF up-regulated by TGF-beta1. CCN2/CTGF stimulated collagen deposition but not collagen synthesis; the collagen mRNA was not increased, suggesting the responsibility of posttranslational events for deposition. It is also important to state that lysyl oxidase activity is enhanced by CCN2/CTGF in cultures of GFs (Hong et al., 1999). Another important finding suggests that CCN2/CTGF effects can be regulated by the MAP kinase pathway, which showed ... [TRUNCATED]