Mechanosignaling pathways in cutaneous scarring

Mechanotransduction is the process by which physical forces are sensed and converted into biochemical signals that then result in cellular responses. The discovery and development of various molecular pathways involved in this process have revolutionized the fundamental and clinical understanding regarding the formation and progression of cutaneous scars. The aim of this review is to report the recent advances in scar mechanosignaling research. The mechanosignaling pathways that participate in the formation and growth of cutaneous scars can be divided into those whose role in mechanoresponsiveness has been proven (the TGF-beta/Smad, integrin, and calcium ion pathways) and those who have a possible but as yet unproven role (such as MAPK and G protein, Wnt/beta-catenin, TNF-alpha/NF-kappa B, and interleukins). During scar development, these cellular mechanosignaling pathways interact actively with the extracellular matrix. They also crosstalk extensively with the hypoxia, inflammation, and angiogenesis pathways. The elucidation of scar mechanosignaling pathways provides a new platform for understanding scar development. This better understanding will facilitate research into this promising field and may help to promote the development of pharmacological interventions that could ultimately prevent, reduce, or even reverse scar formation or progression.