The myofibroblast, cadherin, alpha smooth muscle actin and the collagen effect.

In granulation tissue the myofibroblast, a specialized fibroblast characterized by cytoplasmic stress fibres with alpha smooth muscle actin (SMA), develops from mechano-tension between cells. In vitro the myofibroblast phenotype can be induced in the absence of obvious tension by plating human dermal fibroblasts at low density (LD). Upon reaching confluence the LD-plated cells express alpha SMA within stress fibres. In contrast, few cells express alpha SMA when those same fibroblasts are plated at high density (HD). Cadherins, trans-membrane proteins, and link cells tie the cytoskeletal stress fibres of neighbouring cells together. By immunohistology myofibroblasts (LD-plated fibroblasts) are shown to express cadherin-11 on their surface and between cells, while HD-plated fibroblasts expressed less cadherin-11 on their surface. Western blot analysis revealed elevated concentrations of cadherin-11 and alpha SMA in confluent LD-plated cell lysates. Reduced amounts of both proteins were found in confluent HD-plated cell lysates. Plating fibroblasts on collagen inhibits alpha SMA synthesis. When confluent LD-plated myofibroblasts were covered with a collagen lattice for 24 h, both the expression of cadherin-11 and alpha SMA were reduced by 50%. There is the possibility that direct linkage of the cytoskeleton stress fibres by cell surface cadherins maintains tension between neighbouring cells, which induces alpha SMA expression in stress fibres. Cell contact with collagen reduces cadherin expression, which may eliminate the generation of mechano-tension between fibroblasts. The other possibility is that the myofibroblast phenotype may be induced by factors other than mechano-tension. Copyright 2004 John Wiley & Sons, Ltd.