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41 PROLIFERATION OF PROLIDASE IN KELOID TISSUES
  1. R. Kamdar
  1. Los Angeles, CA

Abstract

Keloids are abnormal scar tissues that expand beyond the wound border. The expansion is marked by an uncontrolled accumulation of collagen consisting of Type I collagen and a hyper-proliferation of fibroblasts. Keloid fibroblasts have been shown to synthesize and secrete collagen as extracellular matrix (ECM) components in response to extrinsic factors. Cytokines such as TNF-α have been shown to reduce ECM deposition by inhibiting the synthesis of structural components i.e., collagen; in contrast, TGF-β stimulates collagen gene expression. Both factors can modulate ECM proteases such as the matrix metalloproteases (MMPs). MMPs degrade collagen fibrils into smaller peptides, which are broken down by an exopeptidase known as prolidase. Prolidase catalyzes the hydrolysis of terminal proline containing end of imidopeptides; thereby, providing free proline as raw materials for newly synthesized collagen.

Objectives To investigate the role of prolidase in the collagen synthesis/degradation process between keloid and normal skin tissues and corresponding fibroblasts; in addition, to examine whether cytokines can modulate this enzyme's activity.

Methods Five matched sets (same donor) of keloid and normal skin tissues were employed. Prolidase activity assay was performed on tissue homogenates. Fibroblasts derived from normal skin and keloid tissues were cultured on plastic dishes as well as on collagen gels. Cultures were exposed to TNF-α, TGF-β, IL-6, and IL-1β, (all at 20 ng/ml) for various time points. Prolidase activity was measured by colorimetric assay.

Results 1) Tissue homogenates showed a significant increase in prolidase activity up to 15-fold difference in keloid tissues as opposed to normal skin. 2) Fibroblast derived from both normal and keloid tissues showed similar proliferative rate. 3) Keloid fibroblasts synthesize more collagen than normal skin in culture. 4) Exposure of fibroblast cell cultures to TGF-β, TNF-α, and interleukins showed an increase in prolidase activity (on both substrates).

Conclusion Keloid tissues contain higher levels of prolidase activity which is also modulated by several cytokines contributing to the fibrotic process.

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