Nov gene encodes adhesion factor for vascular smooth muscle cells and is dynamically regulated in response to vascular injury

Nephroblastoma overexpressed (NOV) is a member of the CCN family (connectiv e tissue growth factor, CYR61, and NOV) of proteins that are involved in re gulating the proliferation, differentiation, and adhesion of a variety of c ell types. We have examined the expression of the Nov gene and NOV protein by vascular smooth muscle cells (VSMCs), in vitro and in vivo, and the effe cts of recombinant NOV on VSMCs, Rat aortic VSMCs were found to express Nov mRNA and NOV protein in vitro and in vivo. Nov expression in adult rat tis sues was very high in the aorta and was detected only weakly in the brain a nd lung by Northern analysis (relative levels 33:3:1). During postnatal dev elopment (3 days to 12 weeks), the expression of Nov was correlated with ma rkers of the differentiated smooth muscle cell phenotype (smooth muscle myo sin heavy chain and SM22 alpha). In the rat carotid artery balloon injury m odel, Nov was detectable by in situ hybridization and was downregulated in the media of the injured artery compared with the uninjured artery at 7 and 14 days after injury. Expression in the developing intima was barely detec table at 7 days after injury except for strong expression at the luminal su rface. At 14 days after injury, Nov expression was substantially increased throughout the intima. In vitro studies of the function of NOV protein show ed that it promoted VSMC adhesion via a mechanism that was divalent cation and Arg-Gly-Asp independent but that it did not modulate VSMC proliferation or phenotype. The strong expression and dynamic regulation of Nov in the a rterial wall, together with its ability to promote VSMC adhesion, suggest t hat it may be involved in homeostasis and repair.