Our overall objective is to understand and alter collagen metabolism in human disease. The normal equilibrium between collagen synthesis and degradation may be lost following tissue trauma, resulting in overabundant (scar) or inadequate collagen deposition (poor wound healing). The rat wound model is used to determine the potential of various pharmacologic agents to restore equilibrium to collagen metabolism. Our unique, accurate method to determine collagen synthesis utilizes C14-proline incorporation and analysis by collagenase digestion. For example, we will determine if colchicine, anti- histamines or corticosteroids diminish collagen synthesis and hence alleviate overabundant scar formation. In contrast, diminished collagen synthesis and poor wound healing that follows therapeutic corticosteroids may be corrected with vitamin A. Agents which will restore equilibrium to collagen metabolism will be adapted for human use when appropriate. Keloids will be used as a model of overabundant collagen deposition in man. Since triamcinolone has been used clinically to suppress keloid formation, the rates of collagen synthesis and degradation will be measured in keloids treated with intralesional triamcinolone. The fibroblast population of keloid and normal skin will be compared by autoradiography and collagen synthesis per fibroblast will be measured. This will determine if therapy should be directed at diminishing collagen synthesis alone, or also at controlling the fibroblast population. Because keloid histamine content is elevated and may stimulate collagen synthesis, we will measure collagen synthesis in rat skin preincubated with histamine and after treatment of rats with 48/80 (a histamine depleter). Because increased soluble keloid collagen may alter the normal feed-back control of collagen synthesis, we will study the effects of a collagen cross-link inhibitor (BAPN) on the rate of collagen synthesis in the rat. These are examples of a animal model being used to understand a human disease.
NIH ExPorter
NIH ExPorter