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 healing seen after glucocorticoid treatment in vivo. Both TGF-beta and glucocorticoids 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, interstitial collagenase and tissue inhibitor of metallo-proteinase-1 (TIMP-1) synthesis at both the protein and mRNA levels in low passage human dermal fibroblasts. Dexamethasone treatment decrease synthesis of procollagen 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 of collagen metabolism away from accumulation. TGF-beta had opposing effects, stimulating both procollagen and TIMP-1 synthesis at the protein and mRNA levels. TGF-beta was able to cause a dose-dependent reversal of the glucocorticoid induced decrease in procollagen and TIMP-1 synthesis. Stimulation of healing in glucocorticoid treated animals by TGF-beta may be by the direct action of this agent upon fibroblast collagen metabolism.