The biology of the myofibroblast

Abstract

The mechanisms leading to the retraction of the granulation tissue during wound healing have not been fully elucidated to date [reviewed in 1]. Our laboratory several years ago described that fibroblasts present in granulation tissue exhibit several ultrastructural features of smooth muscle cells, including the presence of microfilament bundles with dense bodies scattered within [2]. These cells, called myofibroblasts, have been proposed to play a retractile role in several conditions such as granulation tissue contraction, parenchymal organ retraction, fibromatosis and stromal reaction to epithelial tumors [reviewed in 3]. The coincidence of the presence of myofibroblasts with retractile phenomena has supported this hypothesis. However, direct proof of the presence and activity of contractile elements in myofibroblasts has been possible only after suitable techniques have been developed to localize and quantify cytoskeletal and contractile proteins within the affected organs. For this purpose, the advances in the understanding of cytoskeletal and contractile element morphology and biochemistry in different cells have been of great value [reviewed in 4]. Presently, we know that the cytoskeleton of mesenchymal cells is composed of intermediate filaments which consist of a single protein named vimentin. In muscle cells, however, most intermediate filaments have been shown to contain another related, but not identical, protein which is called desmin. However, vascular smooth muscle cells always express vimentin, and only a proportion of them contains in addition desmin. Moreover, desmin has been increasingly found in a number of nonmuscle mesenchymal cells such as endothelial cells [5,6], podocytes [7] and stromal cells from various locations [7-10]. Another marker of tissue origin is the presence of a specific actin isoform, since the six actin isoform expressing mammals show a tissue specific distribution [4]. In particular, α-smooth muscle actin is present in all smooth muscle cells. Finally, isoforms of myosin heavy and light chains can also be typical of smooth muscle (particularly under normal conditions) and hence assist in identifying cells which are involved in different pathological changes [11]