• Journal of Yeungnam Medical Science
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• 제37권2호
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• pp.73-78
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• 2020

Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.

• 생명과학회지
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• 제22권5호
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• pp.569-574
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• 2012

본 연구는 운동 트레이닝이 비만 어린이의 산화적 스트레스, 신경성장 및 간 세포성장 인자에 미치는 영향을 알아보기 위하여 12주간 유산소 운동을 실시한 후 트레이닝 전과 후의 농도 수준을 비교하였다. 연구결과, NGF와 BDNF는 트레이닝 전과 후 모두 OT군이 NT군 보다 낮았으며, NGF는 트레이닝에 따라 두 그룹 모두 증가되었다. HGF는 트레이닝 전 OT군이 NT군 보다 높게 나타났지만, 트레이닝 후 차이는 없었다. MDA, ox-LDL, 8-OHdG 모두 OT군이 NT군 보다 높은 수치를 나타냈고, 트레이닝에 따른 차이는 ox-LDL에서만 발견되었다. 이상의 결과, 비만은 성장기 어린이에게 산화적 스트레스를 유발하고, 신경과 간 성장인자의 분비 이상을 초래한다는 것을 알 수 있었고, 12주 유산소 운동은 이들 인자들의 개선에 긍정적인 영향을 주고 인지기능 향상에도 도움을 줄 수 있을 것으로 본다.

• Animal cells and systems
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• 제2권1호
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• pp.1-8
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• 1998

Hepatocyte growth factor (HGF), originally discovered and cloned as a powerful mitogen for hepatocytes, is a four kringle-containing growth factor which specifically binds to membrane-spanning tyrosine kinase, c-Met/HGF receptor. HGF has mitogenic, motogenic (enhancement of cell movement), morphogenic (e.g., induction of branching tubulogenesis), and anti-apoptotic activities for a wide variety of cells. During embryogenesis, HGF supports organogenesis and morphogenesis of various tissues, including liver, kidney, lung, gut, mammary gland, and tooth. In adult tissues HGF elicits an organotrophic function which supports regeneration of organs such as liver, kidney, lung, and vascular tissues. HGF is also a novel member of neurotrophic factor in nervous systems. Together with the preferential expression of HGF in mesenchymal or stromal cells, and c-Met/HGF receptor In epithelial or endothelial cells, the HGF-Met coupling seems to orchestrate dynamic morphogenic processes through epithelial-mesenchymal (or-stromal) interactions for organogenesis and organ regeneration. HGF or HGF gene may well become unique therapeutic tools for treatment of patients with various organ failure, through its actions to reconstruct organized tissue architectures. This review focuses on recently characterized biological and physiological functions integrated by HGF-Met coupling during organogenesis and organ regeneration.

• KSBB Journal
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• 제18권6호
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• pp.485-489
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• 2003

HGF는 내피세포의 증식 및 이동을 일으키는 강력한 혈관 신생 유도인자 및 생존인자로서 작용한다고 알려져 있다. 본 연구에서는 HUVECs 세포를 이용하여 내피세포의 이동 및 단백질분해효소의 분비에 미치는 HGF의 효과를 확인하였다. 그 곁과, HGF 처리 (10ng/$m\ell$)에 의해 HUVECs 세포의 이동이 약 3.3배 촉진되어, HGF가 HUVECs 세포에서 강력한 이동 유도인자라는 사실을 확인하였다. 내피세포의 이동에 관여할 것이라 여겨지는 MMPs, TIMPs 및 플라스민의 분비에 미치는 HGF의 효과를 관찰한 결과, HGF에 의해 MMP-2 및 MMP-3의 분비양이 각각 3.3배와 6.1배씩 증가되었다. HGF에 의한 TIMPs 분비효과를 관찰한 결과, TIMP-1은 대조군에 비해 약 1.8배 분비가 증가되었으나, TIMP-2는 대조군에 비해 약 3.1배 분비가 억제되었다. 또한, 광범위 MMPs-억제제인 BB-94 (20ng/$m\ell$) 및 플라스민 억제제인 $\alpha$$_2$-antiplasmin (100mU)을 처리했을 때, HGF에 의해 유도된 혈관내피세포의 이동이 거의 완벽하게 억제되었다. 결론적으로, HGF는 HUVECs 세포에서 MMP-2, MMP-3, MMP-9, TIMP-1 및 플라스민의 분비 증가를 일으켰으며, HGF에 의해 분비가 증가 된 단백질분해효소에 의해 세포외기질 및 기저막 단백질로의 혈관내피세포의 이동이 촉진되고, 결과적으로 혈관신생을 유도할 것이라 사료된다.

• 대한의생명과학회지
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• 제30권3호
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• pp.123-130
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• 2024

Mesenchymal stem cells (MSCs) hold great promise as a source of stem cells for therapy, but several limitations remain. We previously proposed that human embryonic stem cell-derived MSCs (hE-MSCs) expressing higher hepatocyte growth factor (HGF) levels were better alternatives, exhibiting greater expandability in vitro and greater therapeutic capacity in vivo. In this study, we aimed to examine the regulation of OCT4 expression in stem cells and to elucidate its underlying mechanism of transcriptional regulation of OCT4. We detected higher expression of OCT4, a stemness-associated gene in hE-MSCs than in human bone marrow-derived MSCs (hBM-MSCs). To determine the underlying regulatory mechanism of OCT4 expression in human MSCs (hMSCs), ELISA was performed using cell culture supernatants of hMSCs. Unlike fibroblast growth factor 2 or vascular endothelial growth factor, HGF was strongly expressed in hE-MSCs, also HGF treatment significantly increased OCT4 expression in hBM-MSC. Moreover, senescence-associated heterochromatin foci were decreased in HGF-treated hBM-MSCs compared with those in the HGF non-treated group. HGF increased Rb phosphorylation, and we confirmed the increased binding of E2F1 to the OCT4 promoter region at -233 from the transcription start point in the presence of HGF. Taken together, these results suggest that HGF-mediated regulation of OCT4 via E2F1 can help enhance the lifespan of hBM-MSCs during in vitro expansion.

• 생명과학회지
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• 제26권10호
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• pp.1189-1195
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• 2016

Vascular endothelial growth factor (VEGF)와 hepatocyte growth factor (HGF)는 강력한 혈관신생 유도인자로 알려져 있다. 세포가 이동하고 침윤하기 위해서는 세포의 증식과 더불어 주변의 세포외기질을 분해하는 단백질분해효소의 분비가 선행되어야 한다. 본 연구에서는 인간의 악성신경교종 유래 세포주인 U-373-MG 세포에 VEGF와 HGF를 처리하여 세포의 증식, matrix metalloproteinase-2 (MMP-2)와 MMP-9 및 플라스민의 분비, 세포의 이동 및 침윤에 미치는 효과를 조사하였다. 또한 단백질분해효소 억제제 처리를 통하여 세포의 증식, 이동 및 침윤에 미치는 단백질분해효소의 역할을 조사하였다. 연구 결과, VEGF와 HGF의 병용처리 시 VEGF와 HGF의 단독 처리 시보다 세포의 증식, MMP-2, MMP-9 및 플라스민의 분비, 세포의 이동 및 침윤이 유의할만하게 증가되었다. 한편 VEGF와 HGF 처리에 의한 U-373-MG 세포의 증식, 이동 및 침윤 증가에 미치는 단백질분해효소의 효과를 MMPs 억제제인 BB-94를 처리하여 조사한 결과 최대 이동 효과를 나타낸 HGF와 VEGF의 병용처리군 보다 세포의 이동이 32% 억제되었고 플라스민 억제제인 α2AP에 의해서도 29% 억제되었다. 또한 U-373-MG 세포의 침윤 역시 BB-94와 α2AP 처리에 의해 유의할 만하게 억제되었다. 이러한 결과는 VEGF와 HGF에 의한 MMP-2, MMP-9 및 플라스민의 분비증가에 의해 직접 또는 간접적인 경로를 통하여 U-373-MG 세포의 증식, 이동 및 침윤을 증가시킨다고 여겨진다.

• Journal of Genetic Medicine
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• 제9권2호
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• pp.78-83
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• 2012

Purpose: The aim of this nested case-control study was to investigate the association between hepatocyte growth factor (HGF) concentrations in maternal plasma and the risk of developing preeclampsia. Materials and Methods: Plasma HGF concentration were measured in 52 women who subsequently developed preeclampsia and 104 normal pregnant women at the time of genetic amniocentesis (15-20 weeks) by enzyme-linked immunosorbent assay. Results: Maternal plasma HGF concentrations were significantly higher in women with subsequent preeclampsia (median: 737.8 ng/mL vs. 670.4 ng/mL, P=0.003) than in normal controls. However, HGF concentrations were not significantly different between subgroups by preeclamptic complications. After adjusting for potential confounding factors, women with HGF concentrations ${\geq}702.5ng/mL$ had a 3.2-fold increased risk (95% CI 2.7-5.4, P<0.001) of subsequent development of preeclampsia compared with women with HGF concentrations <702.5 ng/mL. Conclusion: Elevated maternal plasma HGF concentrations in the early second-trimester are associated with an increased risk of developing preeclampsia.

• IMMUNE NETWORK
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• 제7권3호
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• pp.117-123
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• 2007

Background: This study was designed to investigate the role of the hepatocyte growth factor (HGF) with regards to differentiation of somatic stem cells originating from the human umbilical cord blood (UCB) into hepatic lineage cells in vitro culture system. Methods: Mononuclear cells from UCB were cultured with and without HGF based on the fibroblast growth factor (FGF)-1, FGF-2, and stem cell factor. The cultured cells were confirmed by immunofluorescent staining analysis with albumin (ALB), cytokeratin-19 (CK-19), and proliferating cell nuclear antigen (PCNA) MoAb. ALB and CK-18 mRNA were also evaluated by reverse transcription-polymerase chain reaction. In order to observe changes in proliferating capacity with respect to the cultured period, CFSE with affinity to proliferating cells were tagged and later underwent flow cytometry. Results: In the HGF-treated group, cultured cells had a large oval shaped appearance with adherent, but easily detachable characteristics. In the HGF-non treated group, these cells were spindle-shaped with strong adherent characteristics. Expressions of ALB and CK-19 were evident in HGF-treated group compared to non-expression of those in to HGF-non treated group. Dual immunostaining analysis of the ALB producing cells showed presence of PCNA in their nuclei, and ALB and CK-18 mRNA were detected on the 21st day of cultured cells in the HGF-treated group. Conclusion: Our findings suggest that HGF has a pivotal role in differentiating somatic stem cells of human UCB into hepatic lineage cells in vitro.

• Parasites, Hosts and Diseases
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• 제48권4호
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• pp.291-295
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• 2010

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors and individual host responses to these determinants, In both humans and mice, liver injury is involved after parasite entry, which persists until the erythrocyte stage after infection with the fatal strain Plasmodium falciparum (Pf), Hepatocyte growth factor (HGF) has strong anti-apoptotic effects in various kinds of cells, and also has diverse metabolic functions. In this work, Pf-subtilisin-like protease 2 (Pf-Sub2) 5' untranslated region (UTR) was analyzed and its transcriptional activity was estimated by luciferase expression. Fourteen TATA boxes were observed but only one Oct-1 and c-Myb were done. In addition, host HGF interaction with Pf-Sub2 was evaluated by co-transfection of HGF- and Pf-Sub2-cloned vector. Interestingly, -1,422/+12 UTR exhibited the strongest luciferase activity but -329 to + 12 UTR did not exhibit luciferase activity. Moreover, as compared with the control of unexpressed HGF, the HGF protein suppressed luciferase expression driven by the 5' untranslated region of the Pf-Sub2 promoter. Taken together, it is suggested that HGF controls and interacts with the promoter region of the Pf-Sub2 gene.

• 대한의생명과학회지
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• 제22권1호
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• pp.1-8
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• 2016

Several studies have investigated the various effects of dexamethasone (Dex) on the proliferation and differentiation of mesenchymal stem cells (MSCs). Previously, we reported that co-treatment with L-ascorbic acid 2-phosphate and fibroblast growth factor (FGF)-2 maintained differentiation potential in MSCs through expression of hepatocyte growth factor (HGF). In this study, we investigated the effects of co-treatment with FGF-2 and Dex on the proliferation and differentiation potential of MSCs during a 2-month culture period. Co-treatment with FGF-2 and Dex increased approximately a 4.7-fold higher accumulation rate of MSC numbers than that by FGF-2 single treatment during a 2-month culture period. Interestingly, co-treatment with FGF-2 and Dex increased expression of HGF and maintained adipogenic differentiation potential during this culture period. These results suggest that co-treatment with FGF-2 and Dex preserves the proliferation and differentiation potential during long-term culture.