? Advances in repair are directed at optimizing the closure of chronic wounds and preventing excess scarring in closed wounds. The resolution of chronic wounds by an added growth factor has been disappointing and the search for an agent that prevents or resolves excess scarring continues. During granulation tissue maturation in normal healing wounds, homogeneous populations of fibroblasts share the same phenotype. In early granulation tissue there is the migrating fibroblast, later there is the collagen synthetic fibroblast and during the transition to scar there is the terminal fibroblast undergoing apoptosis. In contrast, chronic wounds and excess scar contains heterogeneous populations of fibroblast phenotypes. Is the failure to synchronize the phenotype of wound fibroblasts contributing to chronic wounds or hypertrophic scars? Through tissue culture models and rat PVA sponge implants, we examined gap junctional intercellular communications (GJIC) in the repair process. Those studies have generated the hypothesis that the synchronization of wound fibroblast phenotypes requires GJIC. Gap junctions are gated channels connecting the cytoplasmic compartments of neighboring cells, which allows molecules less than 1,000 MW to pass. We reported that GJIC between mast cells (MC) and fibroblasts enhances co-cultured MC-fibroblast populated collagen lattices contraction. MCs have bsen implicated in excess scarring. Does GJIC between MCs and fibroblasts contribute to excess scarring? We will document modulation of wound fibroblast phenotypes through GJIC with MCs. In rat PVA sponge implants we reported that agents that disrupt GJIC reduce the deposition of connective tissue around fibroblasts. We recently found that agents, which prevent GJIC between cultured dermal fibroblasts, inhibited the secretion of type I collagen. The Golgi compartment where disruption of GJIC interrupts the translocation of collagen will be identified. The effects of altered GJIC between fibroblasts in PVA sponge implants on the synthesis of collagen and organization of connective tissue will be investigated. The speculation is GJIC coordinates fibroblast phenotypic changes that characterize the progression of the repair process. ? ?
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