SPONTANEOUS KELOID IS CHARACTERIZED BY DISTURBED REGULATION OF TGF-BETA(1) EXPRESSION AND THE COLLAGEN COLLAGENASE BALANCE/

Keloids arise spontaneously as benign tissue masses or at sites of inj ury and are characterized by an abnormal accumulation of extracellular matrix proteins originating from dysregulated fibroblasts. The presen ted case is a spontaneous keloid which had appeared more than 55 years earlier. The aim of the study was to characterize the fibroblasts in terms of their synthesis of collagen and collagenase and the regulator y role of TGF-beta(1). We used fibroblast cultures, Northern hybridiza tion; in situ hybridization and immunohistochemistry. In contrast to t he phenotypically excessive accumulation of connective tissue, the col lagen type I mRNA levels were decreased in fibroblasts outgrown from k eloid areas compared to controls from unaffected areas. At the protein level, collagen synthesis was increased in keloid fibroblasts compare d to controls in vitro. In situ, the mRNA levels for collagen type I w ere increased in the keloid, Furthermore, only minor levels of mRNA fo r interstitial collagenase I were synthesized in keloid fibroblasts in vitro and in situ. In vitro, TGF-beta(1)- incubation increased the co llagen type I mRNA levels in both keloid arid control fibroblasts to a similar extent. However, TGF-beta(1) did not influence the protein le vels of collagen I in keloid fibroblasts, whereas an induction was fou nd in controls. In conclusion, keloid fibroblasts in vitro, experience a disturbed regulation by TGF-beta(1). Furthermore, TGF-beta(1) from island-like cells distributed in the dermis seems to play an essential in vivo role in the maintenance of the disease in this particular cas e. Additionally, the disturbed collagenase regulation causes a decreas ed turnover of collagen and excessive deposition of extracellular matr ix in the pathologically active areas.