THE INTERDEPENDENT MODULATION OF HYALURONAN SYNTHESIS BY TGF-BETA-1 AND EXTRACELLULAR-MATRIX - CONSEQUENCES FOR THE CONTROL OF CELL-MIGRATION

The principal objective of this communication has been to determine the manner in which two tissue culture substrata (plastic dishes and type I collagen gels) modulate the response of adult skin fibroblasts to TGF-beta 1 with respect to hyaluronan (HA) synthesis. Our results indicate that (a) fibroblasts cultured on collagen gels synthesised more HA compared to cells plated at the same density on plastic dishes, (b) this up-regulation in total HA synthesis by collagen-cultured cells was accompanied by an increase in the relative proportion of high molecular mass species of newly synthesised HA, and (c) the specific effect of TGF-beta 1 on HA synthesis was dependent upon the substratum: i.e. TGF-beta 1 inhibited HA synthesis by subconfluent fibroblasts cultured on both substrata, had no apparent effect on confluent cells cultured on collagen gels, and stimulated HA synthesis by confluent cells cultured on plastic dishes. The TGF beta-stimuiation of HA synthesis by confluent fibroblasts cultured on plastic dishes persisted when these cells were transferred to collagen gels in the absence of further TGF-beta 1; interestingly, a second exposure of these plastic pre-incubated cells to TGF-beta 1 whilst growing on collagen resulted in a down-regulation in HA synthesis. Confluent fibroblasts pre-incubated with TGF-beta 1 for 24 h on plastic dishes (i.e. under conditions which stimulate HA synthesis) also displayed an HA-dependent stimulation in cell migration when subsequently plated onto collagen gels in the absence of further cytokine.