title: Hepatoma-derived growth factor is expressed after vascular injury in the rat and stimulates smooth muscle cell migration.
abstract: 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-immunohistochemical 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.
authors.affiliation: Department of Pediatrics, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
authors.forename: Jill V
authors.initials: JV
authors.lastname: Narron
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Stoops
authors.forename: Kurt
authors.initials: K
authors.lastname: Barringhaus
authors.forename: Martin
authors.initials: M
authors.lastname: Matsumura
authors.forename: Allen D
authors.initials: AD
authors.lastname: Everett
mesh_terms: D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000293:injuries*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D020868:Gene Silencing; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor