Molecular cloning and characterization of smlim, a developmentally regulated LIM protein preferentially expressed in aortic smooth muscle cells

Members of the LIM family of zinc-finger proteins have been shown to play an important role in the differentiation of various cell types. By low stringency screening of an aortic library, we have cloned and characterized a developmentally regulated smooth muscle LIM protein, SmLIM, that is expressed preferentially in the rat aorta. This 194 amino-acid protein has two LIM domains, and comparisons of rat SmLIM with its mouse and human homologues reveal high levels of amino acid sequence conservation (100% and 99%, respectively). SmLIM is a nuclear protein and maps to human chromosome 3. SmLIM mRNA expression was high in aorta, low in other smooth muscle tissues such as intestine and uterus, and barely detectable in striated muscle. In contrast with arterial tissue, SmLIM mRNA was barely detectable in venous tissue. During mouse development SmLIM expression was highest at the late primitive streak stage (d 7.5 post coitum), the point at which embryonic and extraembryonic circulations begin to develop. In vitro, SmLIM mRNA levels decreased by 80% in response to PDGF-BB in rat aortic smooth muscle cells. In vivo, SmLIM mRNA decreased by 60% in response to vessel wall injury during periods of maximal smooth muscle cell proliferation. The downregulation of SmLIM by phenotypic changes in vascular smooth muscle cells suggests that it may be involved in their growth and differentiation.