Basic fibroblast growth factor in the extracellular matrix suppresses collagen synthesis and type III procollagen mRNA levels in arterial smooth muscle cell cultures.
To determine the effects of an intact extracellular matrix on collagen synthesis, arterial smooth muscle cells (SMCs) were plated sparsely on a cell-free, SMC-derived matrix and examined the following day. Collagen synthesis during a 5-hour incubation by cells on the matrix was reduced to 67% of the control values obtained from cultures on plastic. Total protein synthesis was unaffected. Treatment of the matrix with heparitinase to remove basic fibroblast growth factor (bFGF) before seeding the SMCs abolished the inhibitory effect of the matrix on collagen synthesis. The inhibitory effect was also eliminated by treating the matrix with a neutralizing polyclonal antibody directed against bFGF. Collagen synthesis by SMC cultures grown in wells coated with purified bFGF was only 61% that of control cultures, whereas total protein synthesis remained unchanged. Slot-blot analysis revealed that the relative message level for alpha 1(III) procollagen was reduced in cultures grown on the preexisting matrix or on plastic precoated with bFGF, whereas the alpha 1(I) procollagen message was unaffected. These results demonstrate the ability of the extracellular matrix to modulate the synthesis of collagen by arterial SMCs and indicate that bFGF in the matrix is responsible for these effects.
Majors
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Research Institute, Cleveland Clinic Foundation, OH 44195.
Ehrhart
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LA
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011347:Procollagen / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*
D011347:Procollagen; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase