Aoyagi M, Yamamoto S, Azuma H, Yamamoto M, Tamaki M, Niimi Y, Hirakawa K, Yamamoto K
Department of Neurosurgery, School of Medicine, Tokyo Medical and Dental University, Japan.
Histochem Cell Biol. 1999 Jun;111(6):419-28. doi: 10.1007/s004180050377.
The migration and proliferation of smooth muscle cells (SMCs) may play a key role in tissue remodeling after arterial wall injury. We investigated the localization and effects of hepatocyte growth factor (HGF) in rabbit carotid arteries after balloon denudation. Immunoreactivity for HGF and the c-Met receptor was clearly observed in neointimal SMCs. The immunoreactivity was not restricted to proliferating cells but was seen even in non-dividing cells in the basal layer of the neointima 4 and 6 weeks after balloon denudation. The distribution of platelet-derived growth factor (PDGF)-positive cells paralleled that of proliferating SMCs. The SMCs in the basal layer of the neointima at 4 and 6 weeks were positive for matrix metalloproteinase (MMP)-2 and membrane type 1-MMP which can activate the proform of MMP-2. HGF significantly stimulated the migration but not proliferation of cultured SMCs. Our results suggest that HGF and PDGF act in coordination to promote the proliferation and migration of SMCs in the earlier phases of neointimal formation and that HGF as well as MMP-2 contribute to the later stages by facilitating the migration but not replication of SMCs.
平滑肌细胞（SMC）的迁移和增殖可能在动脉壁损伤后的组织重塑中起关键作用。我们研究了肝细胞生长因子（HGF）在兔颈动脉球囊剥脱术后的定位及作用。在新生内膜的SMC中可清楚观察到HGF和c-Met受体的免疫反应性。该免疫反应性不仅限于增殖细胞，在球囊剥脱术后4周和6周新生内膜基底层的非分裂细胞中也可见到。血小板衍生生长因子（PDGF）阳性细胞的分布与增殖的SMC平行。在4周和6周时，新生内膜基底层的SMC对基质金属蛋白酶（MMP）-2和可激活MMP-2前体形式的膜型1-MMP呈阳性。HGF显著刺激培养的SMC迁移，但不刺激其增殖。我们的结果表明，HGF和PDGF协同作用以促进新生内膜形成早期SMC的增殖和迁移，并且HGF以及MMP-2通过促进SMC迁移而非复制，在后期发挥作用。
