The deletion of transforming growth factor-beta-induced myofibroblasts depends on growth conditions and actin organization

Myofibroblasts are important but transient mediators of normal wound contra ction and are characterized phenotypically by their high levels of alpha-sm ooth-muscle actin (SMA). During wound maturation, these cells disappear. We have examined the mechanisms that lead to myofibroblast deletion in a fibr oblast culture model. Transforming growth factor-beta (TGF-beta) was used t o increase SMA content in gingival fibroblasts (three- to sixfold). After r eplating TGF-beta-induced cells at low density with serum, there was a five fold decrease in SMA protein content, SMA protein synthesis, and SMA mRNA a s cells proliferated. These reductions were due to reduced SMA mRNA stabili ty. For TGF-beta-induced cells plated at high density without serum tie, qu iescent conditions), protein content was reduced by only 20% over 12 days. TGF-beta protected SMA-positive cells against apoptosis in serum-free cultu res. Those cells that were protected against apoptosis exhibited well-devel oped stress fibers enriched in SMA. We conclude that, in quiescent myofibro blasts, SMA. protein turnover is slow, and cells are long-lived. In prolife rative conditions SMA protein and mRNA turn over quickly, and the myofibrob last phenotype dissipates. The reduced apoptosis of myofibroblasts in quies cent conditions is due in part to the organization of SMA into stress fiber s.