Differential expression of cyclooxygenases in hypertrophic scar and keloid tissues

Abstract

Hypertrophic scar (HS) and keloid (KL) are two forms of an abnormal cutaneous scarring process, mainly characterized by excessive extracellular matrix deposition and fibroblast proliferation. Despite the increased understanding of the molecular and cellular events leading to HS and KL, the pathogenesis of these lesions remains poorly understood. A pivotal role in the formation of abnormal scars has been ascribed to transforming growth factor-beta, whose activity appears to be mediated through a link with pathways acting via cyclooxygenases (COX-1 and COX-2). To date, there is no report on the in vivo expression of COX-1 and COX-2 in human HS and KL tissues. Therefore, using immunohistochemistry and Western blot analysis, we investigated 36 cases of KL, 32 cases of HS, and 25 cases of normal skin in order to define the localization and distribution of COX-1 and COX-2 in the tissues of these scar lesions and the overlying epidermis. The results mainly show the following: (a) a significant overexpression of COX-1 in HS tissues and the overlying epidermis as compared with normal skin and KL tissues and (b) a significant overexpression of COX-2 in KL tissue and the overlying epidermis in contrast to normal skin and HS tissues. Our data support the hypothesis that both COXs are involved in the pathogenesis of scar lesions in different ways and, particularly, COX-1 in the formation of HS and COX-2 in the formation of KL. In addition, the overexpression of COX-1 and COX-2 in the epidermis overlying HS and KL tissues, respectively, underlines the importance of epithelial-mesenchymal interactions in the pathogenesis of scar lesions.