Analysis of the expression and roles of receptor-type tyrosine kinase in keloid tissue

点击翻译按钮获取中文摘要

Keloid is a dermal fibroproliferative tissue of unknown etiology. Protein tyrosine kinases (PTKs) play an important role in the regulation of cell growth and differentiation. Activation of PTK cascade in keloid fibroblasts is thought to be closely linked to abnormal cell proliferation and migration.In order to examine the expression of receptor-type PTK in normal and keloid fibroblasts, we used the homology cloning method with a degenerated primer. Although 8 receptor-type PTK genes were expressed in both fibroblasts, insulin-like growth factor-I receptor (IGF-IR) was overexpressed only in keloid fibroblasts. Immunohistochemical analysis confirmed the high expression of IGF-IR.To examine the functional properties of the IGF-I/IGF-IR pathway, we investigated cell proliferation invasion activity and apoptosis of both types of fibroblasts. The mitogenic effect of IGF-I on both fibroblasts was very weak compared with serum stimulation. In contrast, the invasive activity of keloid fibroblasts was markedly increased in the presence of IGF-I, and inhibited by a neutralizing antibody against IGF-IR. Also keloid fibroblasts resisted apoptosis induced by C2-ceramide. Exogenously added IGF-I enhanced the resistance of keloid fibroblasts to ceramide-induced apoptosis. Wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor suppressed the anti-apoptotic action of IGF-I in keloid fibroblasts.These findings suggest that the involvement of activated IGF-I/IGF-IR signal in the pathogenesis of keloid by enhancing the invasive activity and the resistance to apoptosis of fibroblasts.