Fibroblasts, myofibroblasts, and wound contraction

Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity

“…To assess the contractile potential of fibroblast populations we measured the isotonic contraction of attached collagen gels. Isometrically stressed lattices are a more appropriate model of myofibroblast-populated granulation tissue during wound contraction compared with mechanically unloaded floating lattices (Grinnell, 1994). Isometric tension has been shown to be important for the development of myofibroblastic contractile features such as stress fibers (Burridge, 1981;Tomasek et al, 1992;Katoh et al, 1998;Grinnell et al, 1999a) and ␣-SMA expression in collagen lattices (Arora et al, 1999b).…”

“…To correlate the contractile potential and the level of ␣-SMA expression in cell populations, fibroblasts were grown in attached (Grinnell, 1994) collagen type I lattices (0.75 mg/ml) as previously described (Tomasek et al, 1992;Pilcher et al, 1994;Rayan et al, 1996). Populations were initiated with 0.25-10.0 ϫ 10 5 cells/ml collagen, depending on the presence of serum, the cell type, and the myofibroblastic differentiation, and cultured for 5 d. Lattices populated with transiently transfected 3T3 fibroblast were cultured for 2 d in order to work at their maximum transgene activity, determined by immunofluorescence and Western blotting (see below).…”

“…The main feature of myofibroblasts is represented by an important contractile apparatus similar to that of smooth muscle (Gabbiani et al, 1971), and in particular by the neo-expression of ␣-smooth muscle actin (␣-SMA), the actin isoform typical of vascular smooth muscle cells (Skalli et al, 1986). Myofibroblasts are recognized to play a central role in closing the wound tissue, through their capacity to produce a strong contractile force (for review see Grinnell, 1994;Rønnov-Jessen et al, 1996;Powell et al, 1999;Serini and Gabbiani, 1999), possibly generated within stress fibers, similar to those present in cultured fibroblasts (Skalli et al, 1986;Serini and Gabbiani, 1999). Because wound contraction takes place when de novo expressed ␣-SMA is incorporated in stress fibers (Darby et al, 1990), it has been suggested that this actin isoform plays an important role in granulation tissue contraction (for review see Serini and Gabbiani, 1999).…”

Mechanoregulation of gene expression in fibroblasts

“…However, after a loss of cytoskeletal organization through chemical disruption or through detachment of the gel, which caused cellmediated gel contraction, an upregulation of catabolic gene (MMP-1) expression and inhibition of anabolic gene (α1(I) collagen) expression were observed. The ability of the fibroblasts to remodel their ECM by virtue of an internal contractile mechanism has important implications in wound contracture and connective tissue morphogenesis (Harris et al, 1981;Grinnell, 1994).…”

Transcription factors control invasion: AP-1 the first among equals

“…Long-term responses include the activation of transcription factors that regulate prolonged changes in gene expression (Blatti et al, 1988;Lanahan et al, 1992). Under normal circumstances, when the initiating signal is withdrawn, or the migrating cell reaches its destination, the invasive response attenuates and migratory fibroblasts can differentiate into stationary myofibroblasts that perform discrete wound healing functions (Grinnell, 1994). The signal transduction cascades that are transiently activated by EGF and PDGF in responding cells during wound healing are composed of dominant oncogenic molecules, PDGFR, EGFR, Src, Ras, Raf, mitogen-activated protein (MAP) kinases, Jun kinase (JNK) kinases and PI3 kinase among others.…”