肝细胞生长因子的临床研究及进展

<正>肝细胞生长因子(hepatocyte growth factor,HGF)由各种不同类型的细胞生成,它的组织分布比较广泛,可以参与肝、肺、肾等重要器官细胞的维持和更新,并促进这些器官的再生和损伤后修复,是一种多功能的细胞因子。近几年来,HGF已经引起许多国内外学者的重视,并开始对其进行大量的实验研究,取得了一些新的进展,本文就HGF近年研究进展作如下综述。一、HGF的生物学特性     

肝细胞生长因子与肝细胞再生

肝脏是具有极强再生能力的器官。自Ｈｉｇｇｉｎｓ和Ａｎｄｅｒ－ｓｏｎ报道大鼠部分肝切除术后肝细胞迅速再生实验以来,学者们开展了众多关于肝细胞再生机制的研究。目前,就肝细胞再生启动与终止的机制尚未最终明确。肝细胞增生的过程是通过超乎想象的复杂的调控实现的。肝细胞增生大体可分为３个阶段①增殖启动过程（Ｇ０～Ｇ１期）,相关因子有ＩＬ－１,ＩＬ－６和ＴＮＦ－α;＠增殖促进调节过程（Ｇ１～Ｓ期）,相关因子有肝细胞生长因子（ＨＧＦ）,表皮生长因子（ＥＧＦ）／转化生长因子α（ＴＧＦα）等;③增殖停止过程（Ｇ１～…     

肝细胞生长因子与进展性缺血性脑卒中相关性研究

目的 探讨肝细胞生长因子(HGF)与进展性缺血性脑卒中(SIP)的相关性.方法 选择缺血性脑卒中患者208例,其中SIP组52例、非SIP组156例,SIP组根据病情轻重程度分成轻、中、重型3个水平,根据头部CT扫描结果分为大、中、小梗死灶3个水平,同时选取同期门诊体检的健康者40例为对照组,比较各组间血清HGF浓度,对血清HGF浓度与SIP做相关性分析.结果 SIP组HGF水平高于对照组(P<0.05),随着HGF浓度增高,脑梗死体积越大,神经功能缺损评分越高(P<0.05).结论 SIP患者血清HGF水平升高,可能是预测急性缺血性卒中进展的一个敏感指标,可作为衡量脑梗死程度的敏感指标.     

肝细胞生长因子研究进展

肝细胞坏死性肝炎的预后取决于肝细胞坏死程度和再生能力。70年代学者们集中探索体液因素对肝细胞再生的影响,并分别在血液和肝脏中都发现有促使和抑制肝细胞分裂繁殖的因子存在,这些因子的变化对肝细胞再生起着重要的作用。已陆续发现下述因子有促使肝细胞分裂作用:表皮生长因子     

肝细胞生长因子与肝纤维化关系研究进展

肝细胞生长因子（hepatocyte growth factor,HGF）是一种血源性促肝细胞生长因子,最初是作为一种对成熟肝细胞有明显促生长作用的细胞因子被发现。其具有多种生物学功能,许多实验研究表明,它不仅能促进肝功能的恢复,而且也可以改善肝纤维化。本文将近年来HGF在肝纤维化方面的研究进展综述如下：     

肝细胞生长因子

肝细胞生长因子罗运权吴孟超第二军医大学东方肝胆外科研究所上海市２００４３３ＳｕｂｊｅｃｔｈｅａｄｉｎｇｓＨｅｐａｔｏｃｙｔｅｇｒｏｗｔｈｆａｃｔｅｒＲｅｖｉｅｗｌｉｔｅｒａｔｕｒｅ主题词肝细胞生长因子综述文献中国图书资料分类号Ｒ３４早在１９６４...     

肝细胞生长因子在一些疾病中的变化及意义

肝细胞牛长因子具有多种作用,本文对其近年来在呼吸系统、循环系统、消化系统、泌尿系统等一些疾病发病中的作用及其意义作一综述。     

肝细胞生长因子和器官纤维化

1984年，Nakamura等从部分肝切除大鼠的血清中分离出一种能刺激原代培养的肝细胞生长的因子，并将它命名为肝细胞生长因子（hepatocyte growth factor，HGF）。HGF能通过促进上皮细胞增殖、抑制上皮细胞凋亡及促进胶原降解、抑制胶原合成，参与肝、肾、心、肺等多种器官的结构重建，起器官保护作用，是少数能阻止纤维化的生长因子之一。     

深入对促肝细胞生长物质的研究

深入对促肝细胞生长物质的研究贾克明近年来，从不同乳、幼动物肝脏提取的促肝细胞生长的低分子物质已相当广泛地被用于治疗重症肝炎、慢性肝炎，甚至肝细胞癌，这种努力是值得赞赏的。慢性肝炎的临床表现从极轻到极重千差万别，加之肝炎本身有明显的临床自然治愈倾向，所...     

Hepatocyte growth factor (HGF) and its therapeutic applications

Hepatocyte growth factor (HGF) also known as "scatter factor" (SF), was identified for the first time as a potent mitogen of primary cultured hepatocytes; it has multiple biological responses in a variety of cells including mitogenic, motogenic, morphogenic and antiapoptotic activities. It is secreted as an inactive single chain protein and isproteolitically cleaved to form an active two chain HGF. The hepatocyte growth factor activator (HGFA) is the principal activator of HGF. HGF exerts its biological effects through transmembrane tyrosine kinase receptor (c-Met). HGF is a growth factor displaying a remarkable ability to promote tissue repair and organ regeneration after injury. Therefore attention should be set on the clinical potential of HGF as a treatment for various diseases.     

Hepatocyte growth factor (HGF) in patients with acute brucellosis

In this prospective study, we investigated the serum levels of hepatocyte growth factor (HGF) and C-reactive protein (CRP) before and after the treatment of patients with acute brucellosis. The study comprised 58 patients with acute brucellosis and 30 healthy volunteers. Pre-treatment serum HGF levels of 58 patients with acute brucellosis (1548.6 +/- 220.1) were significantly higher than levels of the control group (401.4 +/- 69.7) (p < 0.001). Serum levels of HGF and CRP significantly decreased at the end of the treatment period (p < 0.001). Post treatment, levels did not differ from those of the control group (p > 0.05). Serum HGF levels of patients with acute brucellosis correlated to CRP and ALT levels (r: 0.922, 0.752; p < 0.001, respectively). Our findings suggest that serum HGF levels may be used as a supplementary marker to evaluate the effectiveness of the treatment in patients with acute brucellosis.     

Hepatocyte growth factor (HGF) in stable and unstable coronary heart disease

Hepatocyte growth factor (HGF) is an angiogenic factor upregulated in ischaemic diseases. We measured plasma HGF concentration in 26 patients (pts) with stable angina pectoris (SAP) and 16 pts with unstable angina pectoris (UAP). HGF levels were significantly higher in pts with UAP compared with pts with SAP (p<0,01), in pts with SAP vs control group (n=38, p<0,01) and in pts with UAP vs control group (p<0,001). HGF levels in SAP group correlated with heart failure symptoms (p=0,023). There was a trend towards significance between HGF and left ventricle ejection fraction (p=0,08) and between HGF and VEGF levels in pts with SAP (p=0,08). This study demonstrates that HGF plasma levels correlates with SAP symptoms. Pts with SAP and UAP has significantly higher levels of HGF comparing with control group.     

Hepatocyte growth factor (HGF) regulates blood-testis barrier (BTB) in adult rats

We have studied the effects of HGF on BTB dynamics in adult rats. We demonstrate that, at stages VII-VIII of the epithelium wave when germ cells traverse the BTB, HGF reduces the levels of occludin and influences its distribution pattern and assembling. Moreover, we report that, at stages VII-VIII, HGF significantly increases the amount of active TGF-β and the amount of uPA present in the tubules. For the first time we report that, in the same stages, HGF reduces the amount of actin present in the BTB region, in which occludin levels are highest, and modifies the morphology of the actin cytoskeleton network. At the level of maximal intensity of occludin fluorescence, we report that HGF also modifies the colocalization of occludin and actin. Lastly, we demonstrate that HGF is maximally expressed at stages VII-VIII, whereas its levels fall in the subsequent stages.     

Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma

Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development against several types of cancer, including glioblastoma, it is important to identify predictive markers that indicate patient subgroups suitable for such therapies. We investigated in vivo glioblastoma models characterized by hepatocyte growth factor (HGF) autocrine or paracrine activation, or by MET or EGFR amplification, for their susceptibility to MET inhibitors. HGF autocrine expression correlated with high phospho-MET levels in HGF autocrine cell lines, and these lines showed high sensitivity to MET inhibition in vivo. An HGF paracrine environment may enhance glioblastoma growth in vivo but did not indicate sensitivity to MET inhibition. EGFRvIII amplification predicted sensitivity to EGFR inhibition, but in the same tumor, increased copies of MET from gains of chromosome 7 did not result in increased MET activity and did not predict sensitivity to MET inhibitors. Thus, HGF autocrine glioblastoma bears an activated MET signaling pathway that may predict sensitivity to MET inhibitors. Moreover, serum HGF levels may serve as a biomarker for the presence of autocrine tumors and their responsiveness to MET therapeutics.     

Hepatocyte growth factor (HGF): A new biochemical marker for acute myocardial infarction

Summary  The purpose of this study was to investigate the use of hepatocyte growth factor as a biochemical marker for acute myocardial infarction. Several biochemical markers are used for noninvasive detection of acute myocardial infarction. However, hepatocyte growth factor has not been used previously for this purpose. We measured hepatocyte growth factor, creatine phosphokinase, and MB isoenzyme (CK-MB) levels in 6 patients with stable effort angina after diagnostic catheterization (controls) and in 12 patients with acute myocardial infarction (AMI). The measurements in the AMI patients were recorded twice a day for the first 3 days after onset of chest pain and once a day for the next 4 days. Furthermore, in each patient we evaluated the time to reach the maximum level and the time for the level to decline to less than half the maximum. Hepatocyte growth factor levels (ng/ml) were 0.3±0.1 for angina pectoris patients, and 15.7±9.1 within 6h and 12.5±4.6 within 12h after the onset for AMI patients, respectively. The correlation coefficients between hepatocyte growth factor and creatine phosphokinase and between hepatocyte growth factor and CK-MB were 0.68 and 0.74, respectively. The time to reach the maximum (h) and the time to decline to less than half of the maximum level (days) were 6.6±2.6 and 1.2±0.2 for hepatocyte growth factor, 19.4±8.7 and 2.5±1.4 for creatine phosphokinase, and 16.6±7.7 and 1.5±0.4 for CK-MB, respectively. Hepatocyte growth factor is useful as a prognostic indicator and reflects the clinical course in patients with acute myocardial infarction.     

Hepatocyte growth factor (HGF) as a potential index of severity of hypertension.

Hepatocyte Growth Factor (HGF) is a mesenchyme-derived pleiotropic factor that regulates cell growth, cell motility, and morphogenesis of various cells, and is thus considered a humoral mediator of epithelial-mesenchymal interactions. We previously identified HGF as a novel member of the family of endothelium-specific growth factors. Moreover, the presence of a local HGF system (HGF and its specific receptor, c-met) has been demonstrated in vascular cells both in vitro and in vivo. HGF might contribute to the protection and/or repair of vascular endothelial cells injured by high blood pressure. If so, serum HGF level might be elevated in response to endothelial cell damage. To test this hypothesis, we measured serum levels of HGF in hypertensive and normotensive patients. Serum HGF concentration in hypertensive patients without any complications was significantly higher than that in normal subjects. Interestingly, serum HGF concentration in hypertensive patients with complications was significantly higher than that in either hypertensive patients without complications or normotensive subjects. Of importance, hypertensive patients treated with antihypertensive drugs showed the same level of serum HGF concentration as normotensive subjects. In contrast, serum HGF concentration in diabetic patients without hypertension was significantly lower than that in normal subjects, whereas serum HGF concentration in diabetic patients with hypertension was significantly higher than that in normal subjects. Moreover, serum HGF concentration in diabetic patients with hypertensive complications was even higher than that in diabetics without complications. This review discusses the possibility that HGF may be considered as a new index of the severity of hypertension.     

Hepatocyte growth factor (HGF) in fecal samples: rapid detection by surface plasmon resonance

Background  

The development of biosensors, based on surface plasmon resonance (SPR) technology, enables monitoring of a variety of biospecific interactions without the need for chemical-, biological- or radiological-labelled reagents.     

Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis

OBJECTIVE: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that has been implicated in cancer growth, tissue development, and wound repair. Its actions are dependent on activation by HGF activator (HGFA) and its binding to a specific HGF receptor (c-Met). We examined the role of HGF, HGFA, and c-Met in synovial tissues in rheumatoid arthritis (RA) and osteoarthritis (OA), and their localization and mRNA expression. METHODS: Immunohistochemical staining, Western blotting, RT-PCR, and in situ hybridization (ISH) for HGF, HGFA, and c-Met were performed on synovial tissue specimens from 10 patients with RA and 4 with OA, and 2 healthy controls. RESULTS: Immunohistochemical staining revealed that HGFA and c-Met were strongly expressed in fibroblasts, macrophages, endothelial cells, and synovial lining cells. HGF was expressed only faintly in macrophages and fibroblasts, and not at all in the endothelial cells of RA and OA synovial tissue. HGFA was detected near 73 and 34 kDa on Western blot analysis, corresponding to inactive and active HGFA, respectively. RT-PCR showed HGF, HGFA, and c-Met mRNA in RA, OA, and control synovial tissue. ISH and immunohistochemistry revealed mRNA expression for HGF, HGFA, and c-Met in the cell types mentioned above. CONCLUSION: HGFA, HGF, and c-Met mRNA are expressed in synovial tissue in RA and OA, and HGF is activated by HGFA and binds to c-Met on endothelial cells, inducing angiogenesis.     

Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: a possible role for HGF in myeloma-associated osteolytic bone disease

Multiple myeloma is associated with unbalanced bone remodeling causing lytic bone lesions. Interleukin-11 (IL-11) promotes osteoclast formation and inhibits osteoblast activity and may, thus, be one factor involved in cancer-induced bone destruction. We have previously shown that myeloma cells produce hepatocyte growth factor (HGF). We now report that HGF induces IL-11 secretion from human osteoblast-like cells and from the osteosarcoma cell lines Saos-2 and HOS. In coculture experiments, both the myeloma cell line JJN-3 and primary myeloma cells from 3 patients induced IL-11 secretion from osteoblasts, whereas no induction was observed with the non-HGF producing myeloma cell line OH-2. Enhanced IL-11 induction was observed with physical contact between osteoblasts and myeloma cells as compared with experiments in which contact was prohibited by tissue inserts. Anti-HGF serum strongly reduced the myeloma cell-induced IL-11 secretion. Furthermore, we show that JJN-3 cells express HGF on the cell-surface. Removal of surface-bound HGF on JJN-3 cells reduced IL-11 production induced in cocultures. Transforming growth factor beta1 and IL-1 potentiated the effect of HGF on IL-11 secretion, whereas an additive effect was observed with tumor necrosis factor. Thus, myeloma-derived HGF can influence the bone marrow environment both as a soluble and a surface-bound factor. Furthermore, HGF emerges as a possible factor involved in myeloma bone disease by its ability to induce IL-11.