• Journal of Oral Medicine and Pain
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• v.31 no.1
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• pp.17-25
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• 2006

The present study was undertaken to determine the possible cellular mechanism of action of angiopoietin-2 in bone metabolism. The effects on the osteoblasts were determined by measuring 1) cell viability, 2) alkaline phosphatase (ALP) activity, 3) gelatinase activity, and 4) nitric oxide production. The effects on the osteoclasts were investigated by measuring 1) tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells (MNCs) formation, and 2) resorption areas after culturing osteoclast precursors. Angiopoietin-2 treatment showed a significant increase in both the viability and ALP activity of osteoblasts. Angiopoietin-2 increased the activity of gelatinase and nitric oxide production. In addition, angiopoietin-2 decreased the osteoclast generation induced by macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL), and inhibited osteoclastic activity in (M-CSF)-dependent bone marrow macrophage (MDBM) cell cultures. Taken these results, angiopoietin-2 may be a regulatory protein within the bone marrow microenvironment.

• The Journal of Korean Society for Radiation Therapy
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• v.12 no.1
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• pp.166-173
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• 2000

Angiopoietin-1(Ang-1) is a vasculogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. We examined the effect of angiopoietin-1(Ang-1) on radiation-induced apoptosis in human umbilical vein endothelial cells(HUVECS) and receptor/second messenger signal transduction pathway for Ang-1's effect on HUVECs. The percent of apoptotic cells under control condition(0Gy) was $8.2\%$. Irradiation induced apoptosis was increased in a dose(1, 5, 10, and 15Gy)- and time 12, 24, 48 and 72hr)-dependent manner. The percent of apoptotic cells was approximately $34.9\%$ after 15 Gy of irradiation. Under these conditions, pretreatment with Ang-1's (50, 100, 200, and 400 ng/ml) inhibited irradiation-induced apoptosis in human umbilical vein endothelial cells in a dose-dependent manner. Two hundred ng/ml of Ang-1 inhibited approximately $55-60\%$ of the apoptotic events that occurred in the 10 Gy-irradiated cells. Pre-treatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the Ang-1's antiapoptotic effects. Phosphatidylinositol 3'-kinase (P13-kinase) specific inhibitor, wortmanin and LY294002, blocked the Ang-1-induced antiapoptotic effect. Ang-1 promotes the survival of endothelial cells in irradiation-induced apoptosis through Tie2 receptor binding and P13-kinase activation. Pretreatment of Ang-1 could be beneficial in maintaining normal endothelial cell integrity during irradiation therapy.

• Clinical and Experimental Reproductive Medicine
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• v.45 no.3
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• pp.143-148
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• 2018

Objective: The favored method of preserving fertility in young female cancer survivors is cryopreservation and autotransplantation of ovarian tissue. Reducing hypoxia until angiogenesis takes place is essential for the survival of transplanted ovarian tissue. The aim of this study was to investigate the role of angiopoietin-1 (Angpt-1), angiopoietin-2 (Angpt-2), and vascular endothelial growth factor (VEGF) in ovarian tissue grafts that were cryopreserved using two methods. Methods: Ovarian tissues harvested from ICR mice were divided into three groups: group I (control), no cryopreservation; group II, vitrification in EFS (ethylene-glycol, ficoll, and sucrose solution)-40; and group III, slow freezing in dimethyl sulfoxide. We extracted mRNA for VEGF, Angpt-1, and Angpt-2 from ovarian tissue 1 week following cryopreservation and again 2 weeks after autotransplantation. We used reverse transcriptase-polymerase chain reaction to quantify the levels of VEGF, Angpt-1, and Angpt-2 in the tissue. Results: Angpt-1 and Angpt-2 expression decreased after cryopreservation in groups II and III. After autotransplantation, Angpt-1 and Angpt-2 expression in ovarian tissue showed different trends. Angpt-1 expression in groups II and III was lower than in group I, but Angpt-2 in groups II and III showed no significant difference from group I. The vitrified ovarian tissues had higher expression of VEGF and Angpt-2 than the slow-frozen ovarian tissues, but the difference was not statistically significant. Conclusion: Our results indicate that Angpt-2 may play an important role in ovarian tissue transplantation after cryopreservation although further studies are needed to understand its exact function.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.178.2-179
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• 2002

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.459-462
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• 2001

Angiopoietin-2 (Ang2) is a naturally occurring antagonist for angiopoietin-l (Angl) and its Tie2 receptor during vasculogenesis, Although angiopoietins have been expressed in several mammalian cell lines, their expression levels are low. Recombinant Chinese hamster ovary (CHO) cell lines expressing a high level of human Ang2 or its analog, human $Ang2_{443}$, with an amino-terminal FLAG-tag were constructed by transfecting the expression vectors into dhfr-deficient CHO cells and subsequent gene amplification in medium containing stepwise increments in methotrexate level. Secreted Ang2 or human $Ang2_{443}$ were purified from the cultured medium using an anti-FLAG- agarose affinity chromatography, The purified Ang2 and $Ang2_{443}$ migrated on SOS-PAGE as a broad band, characteristic of glycosylated protein. Their biological activity in vitro was demonstrated in a serum deprivation-induced apoptosis assay. Ang2 at high concentration, like AngI, can be an apoptosis survival factor for endothelial cells through the activation of the Tie2 receptor.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3405-3409
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• 2016

Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)-1 and Tie-2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang-1-induced proliferation of MPM cells through an NF-kB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells. These results suggest potential clinical use of calpeptin for the treatment of MPM.

• Korean Journal of Exercise Nutrition
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• v.23 no.3
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• pp.39-44
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• 2019

[Purpose] Weight loss can reduce obesity-induced arterial stiffening that is attributed to decreased inflammation. Angiopoietin-like protein 2 (ANGPTL2) is a pro-inflammatory adipokine that is upregulated in obesity and is important in the progression of atherosclerosis and cardiovascular disease. The purpose of this study is to investigate the effects of dietary modification on circulating ANGPTL2 levels and arterial stiffness in overweight and obese men. [Methods] Twenty-two overweight and obese men (with mean age of 56 ± 2 years and body mass index of 28.6 ± 2.6 kg/m²) completed a 12-week dietary modification program. We measured the arterial compliance and β-stiffness index (as the indices of arterial stiffness) and serum ANGPTL2 levels before and after the program. [Results] After the 12-week dietary modification, body mass and daily energy intake were significantly reduced. Arterial compliance was significantly increased and β-stiffness index was significantly decreased after the 12-week dietary modification program. Serum ANGPTL2 levels were significantly decreased. Also, the changes in arterial compliance were negatively correlated with the changes in serum ANGPTL2 levels, whereas the changes in β-stiffness index were positively correlated with the changes in serum ANGPTL2 levels. [Conclusion] These results suggest that the decrease in circulating ANGPTL2 levels can be attributed to the dietary modification-induced reduction of arterial stiffness in overweight and obese men.

• The Korea Journal of Herbology
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• v.27 no.2
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• pp.61-67
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• 2012

Objective : Angelica Gigas Nakai is a popular oriental medicine used for the treatment of vascular diseases. The aim of this study is to investigate neuroprotective effect of the water extract of Anelicae Gigantis Radix Palva (AG) in transient middle cerebral artery occlusion (tMCAO)-induced ischemic rats via the regulation of angiogenesis-related molecules. Methods : Sprague-Dawley rats were intraperitoneally administrated with AG water extract at doses of 10, 25, 50 mg/kg body weight after tMCAO (90 min occlusion). reperfusion for 24 hr infarction volumes were measured by 2,3,5-tetrazolium chloride (TTC) staining. Brain tissues were observed neuronal cell injuries by nissl staining, and also brain-blood barrier (BBB) permeability change by evans blue. Expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Tie-2 receptor protein in brain tissues was determined by western blot. Results : AG water extract significantly reduced infarction volume in ischemic brains of rats, degradation of neuronal cell, BBB permeability and expression of VEGF protein dose-dependently. Ang-1 protein was increased dose-dependantly, not significantly. Conclusion : This study suggests that AG water extract shows neuroprotective effect by preventing BBB breakdown, with regulating angiogenesis factor VEGF and Ang-1.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.5
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• pp.615-623
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• 2016

Angiopoietin-like protein 4 (ANGPTL4) is involved in a variety of functions, including lipoprotein metabolism and angiogenesis. To reveal the role of ANGPTL4 in fat metabolism of sheep, ovine ANGPTL4 mRNA expression was analyzed in seven adipose tissues from two breeds with distinct tail types. Forty-eight animals with the gender ratio of 1:1 for both Guangling Large Tailed (GLT) and Small Tailed Han (STH) sheep were slaughtered at 2, 4, 6, 8, 10, and 12 months of age, respectively. Adipose tissues were collected from greater and lesser omental, subcutaneous, retroperitoneal, perirenal, mesenteric, and tail fats. Ontogenetic mRNA expression of ANGPTL4 in these adipose tissues from GTL and STH was studied by quantitative real time polymerase chain reaction. The results showed that ANGPTL4 mRNA expressed in all adipose tissues studied with the highest in subcutaneous and the lowest in mesenteric fat depots. Months of age, tissue and breed are the main factors that significantly influence the mRNA expression. These results provide new insights into ovine ANGPTL4 gene expression and clues for its function mechanism.

• BMB Reports
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• v.48 no.8
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• pp.429-430
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• 2015

Angiogenesis is a complex process involving dynamic interaction of various cell to cell interactions. Endothelial cell interactions regulated by growth factors, inflammatory cytokines, or hemodynamic stress are critical for balancing vascular quiescence and activation. Yes-associated protein (YAP), an effector of Hippo signaling, is known to play significant roles in maintaining cellular homeostasis. However, its role in endothelial cells for angiogenic regulation remains relatively unexplored. We demonstrated the critical role of YAP in vascular endothelial cells and elucidated the underlying molecular mechanisms involved in angiogenic regulation of YAP. YAP was expressed in active angiogenic regions where endothelial cell junctions were relatively loosened. Consistently, YAP subcellular localization and activity were regulated by VE-cadherin-mediated PI3K/Akt pathway. YAP thereby regulated endothelial sprouting via angiopoietin-2 expression. These results provide an insight into a model of coordinating endothelial junctional stability and angiogenic activation through YAP. [BMB Reports 2015; 48(8): 429-430]