Mechano‐regulation of contractile phenotype in myofibroblasts

Abstract

During wound healing, myofibroblast (MF) appearance correlates with increased wound tension leading to the hypothesis that the mechanics of the wound environment regulate MF formation and function. In this study we examined how the mechanics of a high‐tension environment regulate the MF contractile phenotype. To address this we cultured rat dermal fibroblasts in compliant (low‐tension) and stiff (high‐tension) collagen lattices. Stiff‐cultured cells acquired the MF contractile phenotype of increased focal adhesions and stress fiber bundling and highly expressed the contractile cytoskeletal genes smooth muscle (SM) α‐actin, SM γactin and SM 22‐α. In contrast, compliant‐cultured cells had a fibroblast phenotype and low expression of contractile genes. We next asked if this mechano‐regulation was associated with dynamic changes in the actin cytoskeleton. In support of this, we found induction of F‐actin formation increased contractile gene expression in compliant‐cultured cells, and destabilization of the F‐actin cytoskeleton down‐regulated contractile gene expression in stiff‐cultured cells. We next plan to address the role of the actin‐sensitive transcription factor, myocardin‐related transcription factor‐A, in this process. Our goal is to identify the combination of external and internal factors regulating MF formation, maintenance, and function. Supported by NIH grant R01 GM60651.