TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) AND DEXAMETHASONE HAVE DIRECT OPPOSING EFFECTS ON COLLAGEN-METABOLISM IN LOW PASSAGE HUMAN DERMAL FIBROBLASTS IN-VITRO

Collagen metabolism is a balance between synthesis and lysis. Both are under tight regulatory control. TGF-beta reverse the impairment of he aling seen after glucocorticoid treatment in vivo. Both TGF-beta and g lucocorticoids are known to regulate collagen metabolism directly. We have examined the effect of dexamethasone and of TGF-beta individually and in combination on the regulation of procollagen type 1, interstit ial collagenase and tissue inhibitor of metallo-proteinase-1 (TIMP-1) synthesis at both the protein and mRNA levels in low passage human der mal fibroblasts. Dexamethasone treatment decreased synthesis of procol lagen and caused a dose dependent down-regulation of TIMP-1 synthesis. Interstitial collagenase synthesis by fibroblasts was detectable but low. Thus, glucocorticoid treatment of fibroblasts tilts the balance o f collagen metabolism away from accumulation. TGF-beta had opposing ef fects, stimulating both procollagen and TIMP-1 synthesis at the protei n and mRNA levels. TGF-beta was able to cause a dose-dependent reversa l of the glucocorticoid induced decrease in procollagen and TIMP-1 syn thesis. Stimulation of healing in glucocorticoid treated animals by TG F-beta may be by the direct action of this agent upon fibroblast colla gen metabolism.