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 fib roblasts with respect to the effects of transforming growth factor bet a (TGF-beta) isoforms (-beta 1, -beta 2 and -beta 3) on cell migration and hyaluronan (HA) synthesis. Cell migration was assessed on three-d imensional native type I collagen substrata, Fetal and adult cells dif fered in terms of their motogenic response to the three TGF-beta isofo rms in a manner which was modulated by cell density, i.e.: (1) the mig ration of subconfluent fetal cells was unaffected by TGF-beta 1 and -b eta 2, but inhibited by TGF-beta 3, whilst the migration of subconflue nt adult cells was inhibited by all three isoforms, and (2) the migrat ion of confluent fetal cells was inhibited by all three TGF-beta isofo rms, whilst the migration of confluent adult cells was unaffected by T GF-beta 1 and -beta 2, but stimulated by TGF-beta 3. This diverse patt ern of motogenic response to the three TGF-P isoforms was paralleled b y similar effects on HA synthesis (i.e. inhibition, no effect or stimu lation). Linear regression analysis revealed a significant correlation between cell migration and total HA synthesis (r(2) = 0.861; P < 0.00 01), Gel filtration chromatography of cell-produced HA indicated that the effects of TGF-B isoforms on total HA synthesis reflected alterati ons in the relative production of high molecular mass species (M-r > 1 0(6)). Taken together with previously published data, these observatio ns indicate that (1) fetal and adult fibroblasts exhibit distinct resp onses to the three TGF-P isoforms with respect to both cell migration and HA synthesis, (2) cellular response to the TGF-P isoforms is modul ated by cell density, and (3) TGP-beta 3 is the only isoform which sti mulated cell migration and HA synthesis (with confluent adult cells). (C) 1998 Academic Press Limited.