Post-translational regulation of type I collagen synthesis by heparin in vascular smooth muscle cells.
Heparin is a potent inhibitor of smooth muscle cell proliferation. It reduced the level of type I collagen by one-half in culture medium of smooth muscle cells, whereas it increased the type I collagen expression 4-fold in the cell layer compartment under the conditions where it inhibited cell proliferation. No significant change in the level of prolyl hydroxylation in the newly synthesized type I procollagen or steady-state levels of pro alpha 1 (I) and pro alpha 2 (I) collagen mRNAs was detected after heparin treatment. Short-pulse and pulse-chase experiments revealed that heparin inhibited the secretion of type I procollagen and stimulated the accumulation of type I collagen in the extracellular space. These results suggest that heparin could modulate type I collagen expression at a posttranslational level. The modulation appeared to be closely related with its inhibitory effect on cell proliferation via two different mechanisms: the inhibition of the secretion of type I procollagen and stabilization of type I collagen in the cell layer. Heparin thus appears to be a multifunctional modulator for cell proliferation and the expression of type I collagen in vascular smooth muscle cells.
Tajima
S
S
Department of Dermatology, Keio University School of Medicine, Tokyo.
Wachi
H
H
Takehana
M
M
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015152:Blotting, Northern; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006493:Heparin / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011347:Procollagen / Q000096:biosynthesis / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism
D011347:Procollagen; D012333:RNA, Messenger; D006493:Heparin; D003094:Collagen