Hepatoma-derived growth factor stimulates smooth muscle cell growth and isexpressed in vascular development

Hepatoma-derived growth factor (HDGF) is the first member identified of a n ew family of secreted heparin-binding growth factors highly expressed in th e fetal aorta. The biologic role of HDGF in vascular growth is unknown. Her e, we demonstrate that HDGF mRNA is expressed in smooth muscle cells (SMCs) , most prominently in proliferating SMCs, 8-24 hours after serum stimulatio n. Exogenous HDGF and endogenous overexpression of HDGF stimulated a signif icant increase in SMC number and DNA synthesis. Rat aortic SMCs transfected with a hemagglutinin-epitope-tagged rat HDGF cDNA contain HA-HDGF in their nuclei during S-phase. We also detected native HDGF in nuclei of cultured SMCs, of SMCs and endothelial cells from 19-day fetal (but not in the adult ) rat aorta, of SMCs proximal to abdominal aortic constriction in adult rat s, and of SMCs in the neointima formed after endothelial denudation of the rat common carotid artery. Moreover, HDGF colocalizes with the proliferatin g cell nuclear antigen (PCNA) in SMCs in human atherosclerotic carotid arte ries, suggesting that HDGF helps regulate SMC growth during development and in response to vascular injury.