Alterations in Fibroblast α1β1 Integrin Collagen Receptor Expression in Keloids and Hypertrophic Scars

Abstract

Keloids and hypertrophic scars are significant symptomatic clinical problems characterized by excess collagen. Although extensive research has focused on fibroblasts and collagen turnover in these aberrant scars, little work has been done on the expression of integrins (cell membrane structures that link cells to extracellular matrix) within these lesions. Integrin-mediated regulation of collagen synthesis has previously been observed in explanted fibroblasts from normal and fibrotic dermis, and integrin alpha1 knockout mice maintain increased collagen synthesis consistent with a role for alpha1beta1 in providing negative feedback on collagen synthesis. These findings suggested the need to evaluate integrin roles in keloids and hypertrophic scars. In this study we examined integrin expression in keloids (n = 11), hypertrophic scars (n = 5), radiation ulcers (n = 2), and normal skin specimens (n = 8). We used a novel approach to analysis by isolating dermal fibroblasts directly from tissue (without explant culture) and determining surface integrin expression by flow cytometry. We found that keloids and hypertrophic scars have marked alterations in fibroblast integrin expression and contain several distinct populations of fibroblasts. One of these populations expresses high levels of alpha1 integrin, and the proportion of these cells is higher in keloids (63% +/- 3.6% SEM) and hypertrophic scars (45% +/- 2.7% SEM) than in normal skin tissues (28% +/- 4.7% SEM). The different populations of fibroblasts defined by integrin expression merge, however, when the cells are serially cultured, suggesting that there may be aspects of the dermal microenvironment that maintain the integrin phenotypic heterogeneity in dermal fibroblasts.