FIGURE 7.

Schematic representation of the NO-dependent functional cross-talk between SIRTs and Class I HDACs during skin repair. The schematic shows the class I and III HDAC functional cross-talk important during wound healing. Specifically, SIRT induction by Resv or MC2562 enhances NO production via eNOS activation. Among its pleiotropic functions, NO acts as an inhibitor of HDAC2 via S-nitrosylation. This modification determines the detachment of HDAC2 from the promoter regions of growth factors, including EGF, FGF-10, and IGF-I, relevant to keratinocyte activation. The class I HDAC inhibitors TSA and MS275 or the selective siRNA oligos aimed at HDAC2 knockdown enhanced skin repair. Notably, the Sirtinol inhibition of SIRT activity or the reduction in NO synthesis, determined by L-NAME, retarded wound healing regardless of HDAC2 interference. This evidence suggests that SIRT-dependent NO synthesis plays a dominant role in skin repair.