Increased c-Met phosphorylation is related to keloid pathogenesis: implications for the biological behaviour of keloid fibroblasts

Keloid is induced by a pathological wound healing response, and hepatocyte growth factor (HGF) is known to be involved in tissue repair via the activation of its primary receptor, c-Met. We aimed to investigate whether c-Met activation is implicated in keloid pathogenesis. HGF, c-Met, phosphorylated c-Met (p-Met), Ki-67, collagen I protein, and MET gene expression were detected in five normal skin and 30 keloid tissues by immunohistochemistry and quantitative real-time polymerase chain reaction analysis, respectively. The influence of p-Met expression on the biological behaviour of keloid fibroblasts was further investigated with regard to cell proliferation, motility, invasiveness, collagen I expression, and intracellular signaling in vitro. p-Met protein and MET gene expression but not HGF or c-Met protein expression showed significant increases in keloid tissues than dermal layer of normal skin tissues. In keloid tissues, p-Met expression was significantly associated with keloid size, Ki-67 and collagen I expression. Moreover, p-Met expression was also related to proliferation, migration, invasiveness, collagen I expression and activation of AKT and Erk in keloid fibroblasts in vitro. c-Met activation may have a strong influence on keloid pathogenesis, and it can be investigated further as a potential molecular target for keloid therapy.