FIGURE 2 | The two-stage model of myofibroblast differentiation.

From the following article:

Myofibroblasts and mechano-regulation of connective tissue remodelling

James J. Tomasek, Giulio Gabbiani, Boris Hinz, Christine Chaponnier & Robert A. Brown

Nature Reviews Molecular Cell Biology 3, 349-363 (May 2002)

doi:10.1038/nrm809

Myofibroblasts and mechano-regulation of connective tissue remodelling

In vivo, fibroblasts might contain actin in their cortex but they neither show stress fibres nor do they form adhesion complexes with the extracellular matrix. Under mechanical stress, fibroblasts will differentiate into proto-myofibroblasts, which form cytoplasmic actin-containing stress fibres that terminate in fibronexus adhesion complexes. Proto-myofibroblasts also express and organize cellular fibronectin — including the ED-A splice variant — at the cell surface. Functionally, these cells can generate contractile force. Transforming growth factor beta1 (TGF-beta1) increases the expression of ED-A fibronectin. Both factors, in the presence of mechanical stress, promote the modulation of proto-myofibroblasts into differentiated myofibroblasts that are characterized by the de novo expression of alpha-smooth muscle actin in more extensively developed stress fibres and by large fibronexus adhesion complexes (in vivo) or supermature focal adhesions (in vitro). Functionally, differentiated myofibroblasts generate greater contractile force than proto-myofibroblasts, which is reflected by a higher organization of extracellular fibronectin into fibrils.

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