Effect of Keratinocytes on Myofibroblasts in Hypertrophic Scars

Myofibroblasts play a central role in matrix formation and wound contraction during wound healing and undergo apoptosis at the end of the healing. Hypertrophic scarring is a pathologic condition in which myofibroblasts persist in the tissue. It has been hypothesized that abnormalities in epidermal–dermal crosstalk underlie this pathology. Therefore, in this study, we investigated whether myofibroblasts are affected by keratinocytes. Transforming growth factor beta-induced myofibroblasts (Imyo) and myofibroblasts from hypertrophic scar tissue (Hmyo) were characterized using microarrays. Keratinocytes were co-cultured with myofibroblasts, and quantitative PCR analysis was performed. We found that numerous extracellular matrix- and smooth muscle cell-associated genes were upregulated in Imyo and Hmyo respectively, and these findings suggest that Hmyo are fully differentiated myofibroblasts and that Imyo are less differentiated than Hmyo. Decreased collagen type 1 gene expression was found in keratinocytes co-cultured with Imyo and Hmyo; further, α-smooth muscle actin expression in Imyo increased in the presence of keratinocytes. These observations indicate that keratinocytes play a role in the development of pathological fibrosis in hypertrophic scar tissue by regulating the behavior of dermal fibroblasts and myofibroblasts. We believe that this study provides the basis for understanding the pathophysiology of hypertrophic scarring and identifying new therapeutic approaches for this dysfunction.