The effect of transforming growth factor-beta on cell proliferation and collagen formation by lung fibroblasts.
We examined the effects of transforming growth factor-beta (TGF-beta) on the production of collagen by cultures of human embryonic lung fibroblasts. TGF-beta at 0.1 ng/ml appeared to activate selectively extracellular collagen accumulation as compared with total protein production. A maximal effect inducing a 2-3-fold increase in collagen and total protein production occurred at a dose of 1.0 ng/ml in fibroblast cultures. TGF-beta had no effect on fibroblast proliferation after a 24- and 48-h exposure, including cultures that received a second dose after 24 h. Collagenase digestion of radiolabeled collagen derived from TGF-beta-treated and -untreated cultures revealed no differences in the extent of hydroxylation (37.3 versus 33.4%). TGF-beta increased the production of types I and III collagen without affecting the proportion of collagen types. Fibroblast cultures maintained in medium containing TGF-beta sustained an activated rate of collagen production of 5 nmol/ml/24 h over at least 72 h. We found that epidermal growth factor slightly enhanced TGF-beta-induced collagen formation, whereas TGF-beta increased the proliferative effect of epidermal growth factor. Taken together, these data indicate that collagen production and cell proliferation can be independently regulated and that TGF-beta may have a role in the resolution of tissue injury by stimulating fibroblast-derived collagen synthesis.
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D015291:Transforming Growth Factors; D014633:Valine / Q000378:metabolism
D006133:Growth Substances; D010455:Peptides; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D003094:Collagen; D014633:Valine; D006909:Hydroxyproline