FIG. 1.

Phenotypic changes in fibroblast activation during fibroblast-to-myofibroblast transition (FMT). In response to biochemical signaling, fibroblasts undergo activation. While this activation occurs along a continuous spectrum of phenotypic changes, it can be broadly categorized into three main stages. In the first stage, fibroblasts are quiescent and do not actively remodel the ECM. As they activate, they grow bigger, exhibit more robust stress fibers, and develop mature focal adhesions. Fibroblasts at this stage are categorized as proto-myofibroblasts. Fully activated fibroblasts form supermature focal adhesions and express α-SMA. As the ECM is remodeled by the fibroblasts, mechanical cues including stiffness, stretch, compression, and density increase, further influencing fibroblast activation. Fibroblasts sense and respond to these changes via integrins, G protein-coupled receptors, growth factor receptors, and ion channels. One of the key mechanotransduction pathways underlying fibroblast activation is the integrin-FAK-ROCK-MRTF-YAP-TAZ signaling axis.