Fetal and adult human skin fibroblasts display intrinsic differences in contractile capacity

One of the differences between fetal and adult skin healing is the unique a bility of fetal wounds to heal without contracture and scar formation. Stud ies have shown that the ratio between the three isoforms of TGF beta is dif ferent in adult and fetal wounds. Thus, we analyzed the capacity of adult a nd fetal human skin fibroblasts to contract collagen gels after stimulation with TGF beta isoforms. In control medium, fetal fibroblasts had a contrac tile capacity similar to that of adult fibroblasts. However, the growth cap acity of fetal fibroblasts was completely inhibited, in contrast to adult f ibroblasts. When cells were treated with TGF beta, fetal fibroblasts showed an inhibition of their contractile capacity whereas adult fibroblasts furt her contracted gels. The contractile response was similar for all isoforms of TGF beta although TGF beta3 always had the strongest effect. We consider ed that the regulation of cell contractile capacity by TGF beta may be depe ndent on receptor expression for this cytokine, on myofibroblast differenti ation of the cells, or in eel I links with matrix. Since TGF beta receptor analysis did not show differences in receptor affinity, we studied the expr ession of cc-smooth muscle (SM) actin, a fibroblast contractile marker and of three integrins, the cell surface receptors specific of the attachment o f the fibroblasts with collagen matrix. We observed that the expression of alpha -SM actin and alpha3 and pi integrin subunits was increased when TGFP was added to the medium of adult fibroblasts whereas the levels of the alp ha1 and alpha2 subunits were unchanged. In contrast, fetal fibroblasts trea ted with TGFP showed a decrease of alpha1, alpha2, and pi integrin expressi on but no change in alpha3 integrin and in alpha -SM actin expression. Thes e results indicate that intrinsic differences between fetal and adult fibro blasts might explain their opposite responses to TGF beta stimuli. The vari ations in their a-SM actin and integrin expression patterns represent poten tially important mechanisms used by fetal fibroblasts to regulate their res ponse to cytokines, and likely contribute to the resultant differences in t he quality of wound repair. (C) 2001 Wiley-Liss, Inc.