Everett A D, Lobe D R, Matsumura M E, Nakamura H, McNamara C A
Department of Pediatrics, Cardiovascular Research Center, and. Department of Internal Medicine, Cardiovascular Division, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
J Clin Invest. 2000 Mar;105(5):567-75. doi: 10.1172/JCI7497.
Hepatoma-derived growth factor (HDGF) is the first member identified of a new family of secreted heparin-binding growth factors highly expressed in the fetal aorta. The biologic role of HDGF in vascular growth is unknown. Here, we demonstrate that HDGF mRNA is expressed in smooth muscle cells (SMCs), most prominently in proliferating SMCs, 8-24 hours after serum stimulation. Exogenous HDGF and endogenous overexpression of HDGF stimulated a significant 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 rats, and of SMCs in the neointima formed after endothelial denudation of the rat common carotid artery. Moreover, HDGF colocalizes with the proliferating cell nuclear antigen (PCNA) in SMCs in human atherosclerotic carotid arteries, suggesting that HDGF helps regulate SMC growth during development and in response to vascular injury.
肝癌衍生生长因子（HDGF）是在胎儿主动脉中高度表达的分泌型肝素结合生长因子新家族中首个被鉴定出的成员。HDGF在血管生长中的生物学作用尚不清楚。在此，我们证明HDGF mRNA在平滑肌细胞（SMC）中表达，在血清刺激后8 - 24小时，在增殖的SMC中表达最为显著。外源性HDGF和HDGF的内源性过表达刺激了SMC数量和DNA合成的显著增加。用血凝素表位标记的大鼠HDGF cDNA转染的大鼠主动脉SMC在S期其细胞核中含有HA - HDGF。我们还在培养的SMC细胞核中、19日龄胎儿（而非成年）大鼠主动脉的SMC和内皮细胞核中、成年大鼠腹主动脉缩窄近端的SMC细胞核以及大鼠颈总动脉内皮剥脱后形成的新生内膜中的SMC细胞核中检测到天然HDGF。此外，HDGF与人动脉粥样硬化颈动脉中的SMC增殖细胞核抗原（PCNA）共定位，表明HDGF有助于在发育过程中以及对血管损伤的反应中调节SMC生长。
