Narron Jill V, Stoops Tamara D, Barringhaus Kurt, Matsumura Martin, Everett Allen D
Department of Pediatrics, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Pediatr Res. 2006 Jun;59(6):778-83. doi: 10.1203/01.pdr.0000219299.24435.4f. Epub 2006 Apr 26.
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.
肝癌衍生生长因子（HDGF）作为一种新型的靶向细胞核的血管平滑肌细胞（SMC）有丝分裂原，其在血管损伤中的作用尚不清楚。我们推测，HDGF在大鼠颈动脉球囊损伤后新生内膜形成过程中，对平滑肌细胞增殖和迁移发挥作用。采用免疫组织化学共染色法，在HDGF诱导的颈动脉球囊损伤后7天，80%的新生内膜细胞核中HDGF与增殖细胞核抗原（PCNA）共表达。HDGF阳性的中膜和新生内膜细胞平滑肌肌动蛋白阴性，因此可能代表经历了表型转换的平滑肌细胞亚群。利用改良的博伊登室迁移试验，小鼠平滑肌细胞中腺病毒表达的HDGF使迁移增加了10倍（20比2）。HDGF基因沉默减少了平滑肌细胞的增殖和迁移。总之，HDGF在球囊损伤后的中膜和新生内膜中高表达，是一种平滑肌细胞有丝分裂原和细胞迁移的正调节因子。我们推测，HDGF参与了平滑肌细胞对损伤的增殖和迁移反应，导致新生内膜形成。
