Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-smooth muscle actin within their cytoplasmic stress fibers.

Among these, the EDA isoform of fibronectin (EDA-FN), and collagen type I (COL1A1/COL1A2) are typical markers of myofibroblast-dependent synthesis of pro-fibrotic extracellular matrix.

[3] Together with the co-activation of the non-canonical EGFR pathway, these events lead to upregulation of the ACTA2 gene and subsequent alpha smooth muscle actin protein production.

Several regulators of the myofibroblast differentiation pathway have been described, including hyaluronan and CD44 co-receptor activation of EGFR.

Early work on wound healing showed that granulation tissue taken from a wound could contract in vitro (or in an organ bath) in a similar fashion to smooth muscle, when exposed to substances that cause smooth muscle to contract, such as adrenaline or angiotensin.

Similarly, in wounds that fail to resolve and become keloids or hypertrophic scars, myofibroblasts may persist, rather than disappearing by apoptosis.