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

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).