Insulin-like growth factor-I (IGF-I)/IGF-I receptor axis and increased invasion activity of fibroblasts in keloid

Abstract

Activation of signals for insulin-like growth factor-I receptor (IGF-IR) is thought to be close linked to abnormal cell proliferation and differentiation in various diseases. The keloid in which fibroblasts invade beyond the margins of the original wound, is a dermal fibroproliferative tissue of unknown etiology. Clinically, keloids are most commonly observed in subjects at ages between 10 and 30 years. Interestingly, plasma levels of growth hormone and IGF-I are also high during the same period, suggesting that IGF-I might be involved in the patho-physiology of keloid fibroblasts. We therefore first examined the expression level of IGF-IR in normal and keloid tissues. Immunohistochemical analysis confirmed increased expression of IGF-IR in keloid fibroblasts, but not in normal fibroblasts. On the other hand, the staining intensity of IGF-IR in the epidermis of normal tissues was almost equal to that in keloids. Next, to study the functional properties of the IGF-I/IGF-IR axis in both normal and keloid fibroblasts, we investigated invasion activities. The invasive activity of IGF-IR overexpressing keloid fibroblast was greatly increased in the presence of IGF-I, and inhibited by a neutralizing antibody to IGF-I. In contrast, its activity of IGF-IR weak- expressing normal fibroblasts was not changed. Our results indicate the involvement of the activated IGF-I/IGF-IR axis in the pathogenesis of the invasive activity of fibroblasts.