Regulation of type I collagen and interstitial collagenase mRNA expression in human dermal fibroblasts by colchicine and D-penicillamine.
Sclerosis is a disease process in which idiopathic hardening occurs in the skin and/or internal organs as a result of the accumulation of type I collagen, induced mainly by transforming growth factor-beta. Colchicine and D-penicillamine are widely used for its treatment. Their effects are known to be due to post-translational down-regulation of type I collagen synthesis, with colchicine also up-regulating interstitial collagenase. To determine whether or not they have any pre-translational effect on type I collagen and MMP-1, and also to observe their effects on the action of TGF-beta, cultured neonatal foreskin fibroblasts were treated with colchicine and D-penicillamine, singly and together. The amount of type I collagen and MMP-1 mRNA were quantitated by Northern blot hybridization. Colchicine suppresses the basal level of type I collagen mRNA but minimally stimulates the mRNA expression of MMP-1, whereas D-penicillamine does not have any significant effects on either. Colchicine was also able to significantly suppress the TGF-beta-induced up-regulation of type I collagen mRNA expression.
Chung
K Y
KY
Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea. kychung@yumc.yonsei.ac.kr
Kang
D S
DS
D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology*; D003094:Collagen / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D010396:Penicillamine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D020781:Matrix Metalloproteinase 1; D010396:Penicillamine; D003078:Colchicine