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 injury and are characterized by an abnormal accumulation of extracellular matrix proteins originating from dysregulated fibroblasts. The presented 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 regulatory role of TGF-beta(1). We used fibroblast cultures, Northern hybridization; in situ hybridization and immunohistochemistry. In contrast to the phenotypically excessive accumulation of connective tissue, the collagen type I mRNA levels were decreased in fibroblasts outgrown from keloid areas compared to controls from unaffected areas. At the protein level, collagen synthesis was increased in keloid fibroblasts compared to controls in vitro. In situ, the mRNA levels for collagen type I were increased in the keloid, Furthermore, only minor levels of mRNA for interstitial collagenase I were synthesized in keloid fibroblasts in vitro and in situ. In vitro, TGF-beta(1)- incubation increased the collagen type I mRNA levels in both keloid arid control fibroblasts to a similar extent. However, TGF-beta(1) did not influence the protein levels of collagen I in keloid fibroblasts, whereas an induction was found 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 case. Additionally, the disturbed collagenase regulation causes a decreased turnover of collagen and excessive deposition of extracellular matrix in the pathologically active areas.