Figure 8.

Model of AJ development during fibroblast to myofibroblast transition. (A) Fibroblasts in normal dermis and in mechanically unloaded three-dimensional collagen matrices exhibit a dendritic phenotype and cytoplasmic actin filaments are organized in a submembranous cortex; cells do not develop AJs but communicate via gap junctions (Salomon et al., 1988; Grinnell et al., 2003). (B) Mechanical activation by growth on rigid culture surfaces or tissue matrix reorganization during wound healing leads to the formation of α-SMA–negative stress fibers, i.e., to the development of the proto-myofibroblast (Tomasek et al., 2002; Hinz and Gabbiani, 2003b). Stress fibers of this migratory phenotype are connected to the ECM at sites of FAs and between cells at sites of AJs that predominantly express N-cadherin; few AJs coexpress N-cadherin and OB-cadherin. (C) TGFβ, in the presence of mechanical stress, leads to the further differentiation of myofibroblasts by inducing de novo expression of α-SMA and by increasing expression of OB-cadherin in AJs. The enhanced contractile activity mediated by α-SMA incorporation into stress fibers reinforces AJs and FAs to large supermature contact sites; AJs of differentiated myofibroblasts predominantly express OB-cadherin either exclusively or in conjunction with N-cadherin.