Biological effects of cellular stretch on human dermal fibroblasts

Abstract

Pathological scars are fibroproliferative skin disorders that are characterised by the accumulation of fibroblasts and collagens. It is increasingly understood that their development and progression may be related to local skin mechanics, such as stretching. The present study evaluated the morphological and functional effects of cellular stretch on normal human dermal fibroblasts and explored the mechanotransduction mechanisms that may be involved. When fibroblasts were subjected to 24h of cyclic axial stretching (10cyclesmin(-1)), they migrated faster and for a longer distance than unstretched cells. The increased migration resulted in the cells reorienting themselves perpendicular to the direction of stretching. This was associated with reduced cellular apoptosis and unchanged proliferation. Stretching did not increase collagen synthesis but did elevate collagen degradation. These biological effects appeared to be mediated by the integrin and Wnt mechanotransduction pathways, which transmitted the mechanical stimulus via cell-substrate interactions, cell-cell junctions and indirect cell-cell communications. A better understanding of such fibroblast mechanoresponses invitro will help the development of novel interventions that can prevent, reduce or even reverse pathological scar formation and/or progression invivo.