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KMID : 0578319930030010075
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Molecules and Cells
1993 Volume.3 No. 1 p.75 ~ p.82
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Modulation of collagen Secretion, synthesis and Associated Procollagen mRNA level by colchicine in Human Fibroblasts
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Chung, Moon-Kwan
Kim, In-San/Park, Rang-woon/Jo, Joon-Seung
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Abstract
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Colchicine, an agent that disrupts microtubule formation, has been known to block secretory processes of certain proteins including collagen. Because of this action combined with other biologic effects, colchicine has been suggested as an antifibrotic drug. The present study examined the effect of colchicine on collagen secretion, synthesis and its mRNA levels in cultured human lung fibroblasts. The addition of 0.01 to 25 M concentration of colchicine for 48 h inhibited collagen synthesis in a dose-dependent manner. Unlike collagen synthesis, noncollagen protein synthesis was not strongly affected by the concentrations of colchicine studied. Colcemid, another microtubule disrupting agent, also showed a quite similar result, wherease lumicolchicine, an inactive colchicine, did not A time-dependent study showed that collagen production was apparently reduced by the treatment with 10 pM colchicine between 12- to 18-h of incubation while the inhibition of collagen secretion was noted as early as 3 h after exposure to colchicine. However, upon longer exposure of cultured cells to colchicine, the inhibitory effect on collagen secretion was abolished. Incubation of cultured fibroblasts with colchicine, in the concentration range of 0.1-10 W, resulted in a dose-dependent decrease in the steady-state levels of proal(I) collagen mRNA which was consistent with the protein data. This inhibitory effect on mRNA level was noted as early as 6 h after exposure to colchicine (I W) and abolished by the treatment of cycloheximide. These results suggest that microtubule disruption by colchicine or colcemid specifically inhibits collagen synthesis associated with procollagen mRNA levels and the ability of colchicine to block collagen secretion is only transient.
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KEYWORD
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