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.
Slavin
J
J
Department of Surgery, University of California, San Francisco, USA.
Unemori
E
E
Hunt
T K
TK
Amento
E
E
D015152:Blotting, Northern; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D017364:Collagenases / Q000096:biosynthesis / Q000187:drug effects; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000187:drug effects; D011347:Procollagen / Q000096:biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000502:physiology
D004792:Enzyme Precursors; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011347:Procollagen; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D003094:Collagen; D017364:Collagenases; D008666:Metalloendopeptidases; C022440:procollagenase