Characterization of the Mouse Aortic Carboxypeptidase-Like Protein Promoter Reveals Activity in Differentiated and Dedifferentiated Vascular Smooth Muscle Cells

The dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) contribute to the formation of vascular lesions. In this study, the regulation of aortic carboxypeptidase-like protein (ACLP) expression in VSMCs was investigated. After mouse carotid injury, the expression of ACLP increases in the dedifferentiated VSMCs of the neointima in a pattern that differs from that of smooth muscle α-actin. To better understand the regulation of ACLP in VSMCs, we characterized the 21-exon mouse ACLP gene and 5′-flanking region and examined its promoter activity. In transient transfection assays, 2.5 kb of the ACLP 5′-flanking sequence directed high levels of luciferase reporter activity in primary cultured rat aortic smooth muscle cells, and this activity was not dependent on serum response factor. We identified a positive element between base pairs −156 and −122 by analysis of 5′ deletion and mutant constructs. By use of electrophoretic mobility shift assays with rat aortic smooth muscle cell nuclear ...