Hepatoma-derived growth factor is expressed after vascular injury in the rat and stimulates smooth muscle cell migration

The role of hepatoma-derived growth factor (HDGF), a novel nuclear-targeted vascular smooth muscle cell (SMC) mitogen in vascular injury is unknown. We hypothesized that HDGF plays a role in SMC proliferation and migration in formation of the neointima after balloon injury of the rat carotid. Using co-immumohistochemical staining, HDGF and proliferating cell nuclear antigen (PCNA) were co-expressed in 80% of nuclei of neointimal cells 7 d post carotid balloon injury with HDGF. The HDGF-positive medial and neointimal cells were smooth muscle actin negative and therefore likely represented a subgroup of SMC that have undergone phenotypic switching. Utilizing modified Boyden chamber migration assays, adenoviral-expressed HDGF in mouse SMC increased migration 10-fold (20 versus 2). HDGF gene silencing reduced both SMC proliferation and migration. In conclusion, HDGF is highly expressed in the media and neointima post balloon injury, a SMC mitogen and positive regulator of cell migration. We speculate that HDGF is involved in the SMC proliferative and migratory response to injury resulting in neointimal formation.