© 2000 American Heart Association, Inc.
Vascular Biology |
Nov Gene Encodes Adhesion Factor for Vascular Smooth Muscle Cells and Is Dynamically Regulated in Response to Vascular Injury
From the Section of Cardiovascular Biology (P.D.E., J.C.M., P.R.K.), Department of Biochemistry, and the Physiological Laboratory (Q.C.), University of Cambridge, Cambridge, UK, and the Microchemical Facility (P.J.B.), The Babraham Institute, Cambridge, UK. Dr Chen is now at Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Dr Peter D. Ellis, Section of Cardiovascular Biology, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK. E-mail pde1001{at}mole.bio.cam.ac.uk
Abstract—Nephroblastoma
overexpressed (NOV) is a member of the CCN family (connective tissue
growth factor, CYR61, and NOV) of proteins that are involved in
regulating the proliferation, differentiation, and adhesion of a
variety of cell 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 effects 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 tissues was very high in the aorta and was detected only
weakly in the brain and lung by Northern analysis (relative
levels 33:3:1). During postnatal development (3 days to 12 weeks), the
expression of Nov was correlated with markers of the
differentiated smooth muscle cell phenotype (smooth muscle
myosin heavy chain and SM22
). In the rat carotid artery balloon
injury model, 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 detectable at 7 days
after injury except for strong expression at the luminal surface. At 14
days after injury, Nov expression was substantially
increased throughout the intima. In vitro studies of the function of
NOV protein showed 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
arterial wall, together with its ability to promote VSMC
adhesion, suggest that it may be involved in homeostasis and
repair.
Key Words: Nov gene • CCN family • gene expression • balloon injury
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