Mars W M, Liu M L, Kitson R P, Goldfarb R H, Gabauer M K, Michalopoulos G K
Department of Pathology, University of Pittsburgh School of Medicine, PA 15261, USA.
Hepatology. 1995 Jun;21(6):1695-701.
Hepatocyte growth factor (HGF), also known as scatter factor, is believed to play a primary role in liver regeneration. HGF is produced in an inactive single-chain form that can be cleaved in vitro to the active two-chain form by tissue-type and urokinase-type plasminogen (PLG) activators (tPA and uPA). We have now documented the de novo appearance of active uPA in livers from male Fischer F344 rats that underwent 70% partial hepatectomy (PHx) as early as 1 minute after surgery. Western blot analyses of protein extracts from liver remnants that were obtained immediately after surgery and periodically until 24 hours after PHx indicate that the quantity of uPA remains fairly constant in PHx samples. In contrast, the uPA receptor (uPAR) dramatically increases, beginning within 1 minute after PHx. This results in enhanced activity of uPA, as seen by direct zymography on cryostat sections. The uPA present in remnant liver homogenates from rats that underwent PHx is the primary agent that cleaves single-chain HGF to its two-chain form, because cleavage can be prevented when antibody against uPA is included in the liver homogenates. Furthermore, heterodimeric HGF, which is not present in normal liver, increases in the liver remnants from rats that underwent PHx, correlative to uPAR. The presence of active uPA is one of the earliest responses yet documented after PHx. These findings imply that both uPA and uPAR are involved in activating endogenous HGF in the regenerating livers of animals that underwent PHx.
肝细胞生长因子（HGF），也被称为分散因子，被认为在肝脏再生中起主要作用。HGF以无活性的单链形式产生，在体外可被组织型和尿激酶型纤溶酶原（PLG）激活剂（tPA和uPA）切割成有活性的双链形式。我们现已证明，在接受70%部分肝切除术（PHx）的雄性Fischer F344大鼠肝脏中，早在手术后1分钟就出现了活性uPA的重新合成。对手术后立即获取并定期采集直至PHx后24小时的肝残余物蛋白质提取物进行的蛋白质印迹分析表明，PHx样本中uPA的量保持相当恒定。相比之下，uPA受体（uPAR）在PHx后1分钟内开始显著增加。这导致uPA活性增强，如在低温恒温器切片上直接进行酶谱分析所见。接受PHx的大鼠肝残余物匀浆中存在的uPA是将单链HGF切割成双链形式的主要因子，因为当肝匀浆中包含抗uPA抗体时，切割可被阻止。此外，正常肝脏中不存在的异二聚体HGF在接受PHx的大鼠肝残余物中增加，与uPAR相关。活性uPA的存在是PHx后迄今记录到的最早反应之一。这些发现表明，uPA和uPAR都参与了在接受PHx的动物再生肝脏中激活内源性HGF的过程。
