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

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Abstract
One of the differences between fetal and adult skin healing is the unique ability of fetal wounds to heal without contracture and scar formation. Studies have shown that the ratio between the three isoforms of TGFβ is different in adult and fetal wounds. Thus, we analyzed the capacity of adult and fetal human skin fibroblasts to contract collagen gels after stimulation with TGFβ isoforms. In control medium, fetal fibroblasts had a contractile capacity similar to that of adult fibroblasts. However, the growth capacity of fetal fibroblasts was completely inhibited, in contrast to adult fibroblasts. When cells were treated with TGFβ, fetal fibroblasts showed an inhibition of their contractile capacity whereas adult fibroblasts further contracted gels. The contractile response was similar for all isoforms of TGFβ although TGFβ3 always had the strongest effect. We considered that the regulation of cell contractile capacity by TGFβ may be dependent on receptor expression for this cytokine, on myofibroblast differentiation of the cells, or in cell links with matrix. Since TGFβ receptor analysis did not show differences in receptor affinity, we studied the expression of α‐smooth muscle (SM) actin, a fibroblast contractile marker and of three integrins, the cell surface receptors specific of the attachment of the fibroblasts with collagen matrix. We observed that the expression of α‐SM actin and α3 and β1 integrin subunits was increased when TGFβ was added to the medium of adult fibroblasts whereas the levels of the α1 and α2 subunits were unchanged. In contrast, fetal fibroblasts treated with TGFβ showed a decrease of α1, α2, and β1 integrin expression but no change in α3 integrin and in α‐SM actin expression. These results indicate that intrinsic differences between fetal and adult fibroblasts might explain their opposite responses to TGFβ stimuli. The variations in their α‐SM actin and integrin expression patterns represent potentially important mechanisms used by fetal fibroblasts to regulate their response to cytokines, and likely contribute to the resultant differences in the quality of wound repair.

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