Myofibroblasters

Myofibroblasters are specialized contractile cells derived from resident fibroblasts and other precursor cells that acquire smooth muscle–like features, most notably expression of alpha-smooth muscle actin (α-SMA). They synthesize extracellular matrix and generate contractile force during tissue repair, and their presence marks granulation tissue and wound contraction.

Origin and activation. They originate primarily from resident fibroblasts but can arise through epithelial-to-mesenchymal or endothelial-to-mesenchymal transitions, pericytes, or circulating fibrocytes. Activation is driven by transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and mechanical cues from a stiffened extracellular matrix, via signaling pathways such as RhoA/ROCK that promote actin remodeling.

Physiological role. In normal healing, myofibroblasts deposit collagen types I and III and fibronectin, remodel the ECM, and generate forces that contract the wound. After closure, they typically undergo apoptosis or revert to a quiescent fibroblast phenotype; failure to resolve their activity can cause excessive scar formation.

Pathology. Persistent myofibroblast activation contributes to fibrosis in organs including the liver, lungs, kidneys, and skin. Chronic activation leads to excessive extracellular matrix deposition, tissue stiffening, and impaired function; in the skin, this can manifest as hypertrophic scars or keloids.

Markers and detection. α-SMA is the principal marker of myofibroblasts, with coexpression of vimentin and ECM components such as collagen I, collagen III, and fibronectin. Marker expression can vary by context, and identification often relies on a combination of signals.

Clinical relevance. Research targets myofibroblast activation, persistence, and survival to treat fibrotic diseases. Therapeutic approaches include antifibrotic drugs and inhibitors of TGF-β signaling, as well as strategies that modify matrix stiffness or promote myofibroblast apoptosis.