Controlling the expression of smooth muscle contractile protein isoforms: a role for the extracellular matrix?

Abstract

Whereas the controlling genetic elements governing the commitment and differentiation of skeletal muscle have been reasonably well characterized (for a recent review, see reference 1), such detailed information regarding similar events in smooth muscle is lacking. In spite of this, a growing body of information indicates that the extracellular matrix and its associated growth regulators play pivotal roles in modulating smooth muscle cell growth and contractile phenotype during developmental and disease processes, including the response to injury (2, 3). Further support for the role that cell-cell and cell-matrix interactions play in modulating smooth muscle contractile phenotype comes from the report in this issue by Mitchell and colleagues (4). Data demonstrate that the expression of a-smooth muscle actin can be altered in fibroblastic cells derived from rat lung, and modulation of isoactin expression is dependent upon culture conditions. Notably, and in common with the aortic smooth muscle cell and the pericyte (the smooth muscle cell counterpart ofthe microcirculation [5]), the rat smooth muscle-like cells express an abundance of a-smooth muscle cell actin when cultures are confluent. However, while proliferating, the lung fibroblast phenotype is more closely aligned with a non-muscle cell. This observation, too, is consistent with what is seen in the mural (vascular smooth muscle and pericyte) cell counterparts. Additionally, Mitchell and colleagues demonstrate that transforming growth factor-S, a component of the extracellular matrix, is capable of shifting the lung cell phenotype from the non-muscle to the smooth muscle as evidenced by the accumulation of smooth muscle cell contractile protein isoforms. This, too, has parallels in the microvasculature since activation of latent lGF-J3, an event that is specifically dependent upon contact between endothelial cells and pericytes, results in endothelial growth arrest (6). These in vitro findings are consistent with the notion that the .levels of smooth muscle contractile proteins expressed within the lung parenchyma may modulate during disease.