Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability.
Transforming growth factor-beta (TGF-beta) has been shown to stimulate synthesis of extracellular matrix proteins, both in animals and in cell culture. We found that mRNAs for alpha 1(I) collagen, fibronectin, and thrombospondin were markedly increased in TGF-beta-treated 3T3 (mouse) cells. For collagen and fibronectin this increase was 10-to 20-fold, as measured by quantitative blot hybridization analysis. A maximal value was reached at 16-24 hr, with a subsequent gradual decline. Concomitant treatment with cycloheximide prevented the stimulation observed with TGF-beta. Under conditions of confluent growth a clear increase in alpha 1(I) collagen mRNA stability was observed, whereas in subconfluent cells no change in mRNA half-life was found, despite an equally large increase in mRNA levels. We suggest that the mode of action of TGF-beta varies with the target cell and depends on the interplay of a number of complex cellular factors.
Department of Biochemistry, University of Washington, Seattle 98195.
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Penttinen
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Kobayashi
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Bornstein
D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D013268:Stimulation, Chemical; D019699:Thrombospondins; D015291:Transforming Growth Factors
D005353:Fibronectins; D006023:Glycoproteins; D010455:Peptides; D012333:RNA, Messenger; D019699:Thrombospondins; D015291:Transforming Growth Factors; D003094:Collagen