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Cytokine. 1998 Apr;10(4):281-9.

Differential motogenic and biosynthetic response of fetal and adult skin fibroblasts to TGF-beta isoforms.

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Department of Dental Surgery and Periodontology, Dental School, University of Dundee, UK.


Data are presented in this communication comparing fetal and adult fibroblasts with respect to the effects of transforming growth factor beta (TGF-beta) isoforms (-beta 1, -beta 2 and -beta 3) on cell migration and hyaluronan (HA) synthesis. Cell migration was assessed on three-dimensional native type I collagen substrata. Fetal and adult cells differed in terms of their motogenic response to the three TGF-beta isoforms in a manner which was modulated by cell density, i.e.: (1) the migration of subconfluent fetal cells was unaffected by TGF-beta 1 and -beta 2, but inhibited by TGF-beta 3, whilst the migration of subconfluent adult cells was inhibited by all three isoforms, and (2) the migration of confluent fetal cells was inhibited by all three TGF-beta isoforms, whilst the migration of confluent adult cells was unaffected by TGF-beta 1 and -beta 2, but stimulated by TGF-beta 3. This diverse pattern of motogenic response to the three TGF-beta isoforms was paralleled by similar effects on HA synthesis (i.e. inhibition, no effect or stimulation). Linear regression analysis revealed a significant correlation between cell migration and total HA synthesis (r2 = 0.861; P < 0.0001). Gel filtration chromatography of cell-produced HA indicated that the effects of TGF-beta isoforms on total HA synthesis reflected alterations in the relative production of high molecular mass species (M(r) > 10(6)). Taken together with previously published data, these observations indicate that (1) fetal and adult fibroblasts exhibit distinct responses to the three TGF-beta isoforms with respect to both cell migration and HA synthesis, (2) cellular response to the TGF-beta isoforms is modulated by cell density, and (3) TGF-beta 3 is the only isoform which stimulated cell migration and HA synthesis (with confluent adult cells).

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