Insulin-like growth factor-I (IGF-I)/IGF-I receptor axis and increased invasion activity of fibroblasts in keloid.
Activation of signals for insulin-like growth factor-I receptor (IGF-IR) is thought to be closely 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 fibroblasts 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.
Ohtsuru
A
A
Department of Nature Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Japan.
Yoshimoto
H
H
Ishihara
H
H
Namba
H
H
Yamashita
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D007627:Keloid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012016:Reference Values
D000906:Antibodies; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1