• Molecules and Cells
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• v.20 no.2
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• pp.263-270
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• 2005

Transactivation of EGF-receptor (EGFR) by G-protein coupled receptors (GPCRs) is emerging as an important pathway in cell proliferation, which plays a crucial role in the development of atherosclerotic lesion. Angiotensin II (Ang II) has been identified to have a major role in the formation of atherosclerotic lesions, although the underlying mechanisms remain largely unclear. We hypothesize that Ang II promotes the proliferation and migration of smooth muscle cells through the release of heparin-binding epidermal growth factor like growth factor (HB-EGF), transactivation of EGFR and activation of Akt and Erk 1/2, with matrix metalloproteases (MMPs) playing a dispensable role. Primary rat aortic smooth muscle cells were used in this study. Smooth muscle cells rendered quiescent by serum deprivation for 12 h were treated with Ang II (100 nM) in the presence of either GM6001 ($20{\mu}M$), a specific inhibitor of MMPs or AG1478 ($10{\mu}M$), an inhibitor of EGFR. The levels of phosphorylation of EGFR, Akt and Erk 1/2 were assessed in the cell lysates. Inhibition of MMPs by GM6001 significantly attenuated Ang II-stimulated phosphorylation of EGFR, suggesting that MMPs may be involved in the transactivation of EGFR by Ang II receptor. Furthermore Ang II-stimulated proliferation and migration of smooth muscle cells were significantly blunted by inhibiting MMPs and EGFR and applying HB-EGF neutralization antibody, indicating that MMPs, HB-EGF and EGFR activation is necessary for Ang-II stimulated migration and proliferation of smooth muscle cells. Our results suggest that inhibition of MMPs may represent one of the strategies to counter the mitogenic and motogenic effects of Ang II on smooth muscle cells and thereby prevent the formation and development of atherosclerotic lesions.

• Bulletin of the Korean Chemical Society
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• v.35 no.4
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• pp.1036-1042
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• 2014

In this study, we introduced the RRLR oligopeptide sequences on the surface of polyamidoamine (PAMAM) dendrimer and characterized the physical properties and gene carrier activity of the novel polymer using HEK 293, NIH3T3, and HeLa cells. The RRLR peptide sequences were derived from a mouse fibroblast growth factor 3 (FGF3) protein containing a bipartite NLS motif. The entire sequence of FGF3 is RLRRDAGGRGGVYEHLGGAPRRRK and it has two functional sequences RLRR and RRRK at N-terminus and C-terminus, respectively. In particular, PAMAM G4-RRLR conferred enhanced transfection efficiency and lower cytotoxicity compared with those of PEI 25 kDa, PAMAM G4-R, and PAMAM G4 in various cell lines. These results suggest that the introduction of N-terminal oligopeptides of FGF3 on the surface of PAMAM holds promise as an effective non-viral gene delivery carrier for gene therapy.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1227-1233
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• 2015

Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis through binding to its specific receptors, which mainly occurs to VEGF receptor 2 (VEGFR-2), a kinase insert domain-containing receptor. Therefore, the disruption of VEGFR-2 signaling provides a promising therapeutic approach for the treatment of cancer by inhibiting abnormal or tumorinduced angiogenesis. To explore this potential, we expressed the catalytic domain of VEGFR-2 (VEGFR-2-CD) as a soluble active kinase in Escherichia coli. The recombinant protein was purified and the VEGFR-2-CD activity was investigated. The obtained VEGFR-2-CD showed autophosphorylation activity and phosphate transfer activity comparable to the commercial enzyme. Furthermore, the IC₅₀ value of known VEGFR-2 inhibitor was determined using the purified VEGFR-2-CD. These results indicated a possibility for functional and economical VEGFR-2-CD expression in E. coli to use for inhibitor screening.

• Animal Bioscience
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• v.34 no.11
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• pp.1802-1810
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• 2021

Objective: The purpose of this study was to evaluate the effects of supplementing herbal active ingredients (YGF251) which can promote the secretion of insulin-like growth factor-1 (IGF-1) in the diet on production performance, egg quality, blood hematology, and excreta gas emission in laying hens. Methods: A total of 288 ISA Brown (41-week-old) laying hens with an initial body weight of 1.83±0.68 kg were randomly assigned to 1 of 4 dietary treatments in a randomized block design based on body weight. Each treatment had 12 replicate cages having 6 adjacent cages per replicate (hens are kept in cages alone). The experimental period was 35 days. Dietary treatments were based on the corn-soybean meal-wheat-based basal diet and supplemented with 0.00%, 0.05%, 0.10%, or 0.15% YGF251. Results: There was a linear increased egg weight in weeks 1 to 5 (p<0.05), egg mass in week 1 (p<0.05) and weeks 1 to 5 (p<0.05), egg strength on day 7 (p<0.05), 21 (p<0.01), and 35 (p<0.01), eggshell thickness on day 21 (p<0.05) and 35 (p<0.01), haugh unit on day 21 (p<0.01) and 35 (p<0.05), serum IGF-1 concentration on day 21 (p<0.05) and 35 (p<0.01), and serum total protein concentration on day 35 (p<0.05) were observed with the supplementing YGF251 increased in the diet, while feed conversion ratio in weeks 1 to 5 (p<0.05) and excreta ammonia emission (p<0.01) decreased linearly with the dose of YGF251 increased. Conclusion: Dietary supplementation of YGF251 positively affected the production performance and egg quality of laying hens through increasing serum IGF-1 concentration in a dose-dependent manner. Moreover, YGF251 supplementation improved barn environment by reducing excreta noxious gas emission.

• Molecules and Cells
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• v.42 no.11
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• pp.763-772
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• 2019

Periodontitis is characterized by the loss of periodontal tissues, especially alveolar bone. Common therapies cannot satisfactorily recover lost alveolar bone. Periodontal ligament stem cells (PDLSCs) possess the capacity of self-renewal and multilineage differentiation and are likely to recover lost alveolar bone. In addition, periodontitis is accompanied by hypoxia, and hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) is a master transcription factor in the response to hypoxia. Thus, we aimed to ascertain how hypoxia affects runt-related transcription factor 2 (RUNX2), a key osteogenic marker, in the osteogenesis of PDLSCs. In this study, we found that hypoxia enhanced the protein expression of $HIF-1{\alpha}$, vascular endothelial growth factor (VEGF), and RUNX2 ex vivo and in situ. VEGF is a target gene of $HIF-1{\alpha}$, and the increased expression of VEGF and RUNX2 proteins was enhanced by cobalt chloride ($CoCl_2$, $100{\mu}mol/L$), an agonist of $HIF-1{\alpha}$, and suppressed by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1, $10{\mu}mol/L$), an antagonist of $HIF-1{\alpha}$. In addition, VEGF could regulate the expression of RUNX2, as RUNX2 expression was enhanced by human VEGF ($hVEGF_{165}$) and suppressed by VEGF siRNA. In addition, knocking down VEGF could decrease the expression of osteogenesis-related genes, i.e., RUNX2, alkaline phosphatase (ALP), and type I collagen (COL1), and hypoxia could enhance the expression of ALP, COL1, and osteocalcin (OCN) in the early stage of osteogenesis of PDLSCs. Taken together, our results showed that hypoxia could mediate the expression of RUNX2 in PDLSCs via $HIF-1{\alpha}$-induced VEGF and play a positive role in the early stage of osteogenesis of PDLSCs.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.707-711
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• 1998

The (Na,K)ATPase is responsible for generating the ionic gradients and membrane potentials by the exchange of intracellular $Na^+$ for $K^+$. It has been recentl y shown that (Na,K)ATPase is involved in the exocytic pathway of basic fibroblast growth factor (bFGF), although it is not known that bFGF is secreted to the outside of cell through direct interaction with (Na,K) ATPase. To understand the role for (Na,K)ATPase in the secretary pathway of bFGF, we have sought to identify the cytoplasmic domains of the alpha1 isoform of (Na,K)ATPase interacting with bFGF by yeast two-hybrid system. We have also investigated the interaction between the alpha2 isoform of (Na,K)ATPase and bFGF to find out whether the interaction is isoform-specific. We found that none of the cytoplasmic domains of (Na,K)ATPase isoforms interacted with bFGF. The result suggests that the interaction between bFGF and (Na,K)ATPase might be indirect, thus requiring other proteins which are involved in the formation of protein complexes for the interaction, although we cannot exclude the possibility that the interaction requires the element of the whole alpha subunit structure that was not present in the isolated alpha subunit cytoplasmic domains.

• BMB Reports
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• v.40 no.2
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• pp.180-188
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• 2007

In vivo studies have demonstrated that aldosterone is an independent contributor to glomerulosclerosis. In the present study, we have investigated whether aldosterone itself mediated glomerulosclerosis, as angiotensin II (Ang II) did, by inducing cultured renal mesangial cells to produce plasminogen activator inhibitor-1 (PAI-1), and whether these effects were mediated by aldosterone-induced increase in transforming growth factor $\beta_1$ (TGF-$\beta_1$) expression and cellular reactive oxygen species (ROS) activity. Quiescent rat mesangial cells were treated by aldosterone alone or by combination of aldosterone and spironolactone, Ang II, neutralizing antibody to TGF-$\beta_1$ or antioxidant Nacetylcysteme (NAC). This study indicate that aldosterone can increase PAI-1 mRNA and protein expression by cultured mesangial cells alone, which is independent of aldosterone-induced increases in TGF-$\beta_1$ expression and cellular ROS. The effects on PAI-1, TGF-$\beta_1$ and ROS generation were markedly attenuated by spironolactone, a mineralocorticoid receptor antagonist, which demonstrate that mineralocorticoid receptor (MR) may play a role in mediating these effects of aldosterone.

• Journal of Mushroom
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• v.12 no.2
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• pp.77-81
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• 2014

Mushrooms are considered not only as food but also for source of physiologically beneficial medicines. The culinary-medicinal mushrooms may important role in the prevention of age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Hericium erinaceus (H. erinaceus), is edible mushrooms, is a parasitic fungus that grows hanging off of logs and trees and well established candidate for brain and nerve health. H. erinaceus contains high amounts of antioxidants, beta-glucan, polysaccharides and a potent catalyst for brain tissue regeneration and helps to improve memory and cognitive functions. Its fruiting bodies and the fungal mycelia exhibit various pharmacological activities, including the enhancement of the immune system, antitumor, hypoglycemic and anti-aging properties. H. erinaceus stimulates the synthesis of Nerve Growth Factor (NGF) which is the primary protein nutrient responsible for enhancing and repairing neurological disorders. Especially hericenones and erinacines isolated from its fruitin body stimulate NGF, synthesis. This fungus is also utilized to regulate blood levels of glucose, triglycerides and cholesterol. H. erinaceus can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro, in vivo and clinical trials for neurodegerative disease.

• The Korean Journal of Food And Nutrition
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• v.22 no.3
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• pp.416-420
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• 2009

A formula diet based on pork meat oligopeptides(pork meat protein hydrolysates) was designed for experimental hepatitic rats. The rats were given D-galactosamine for 6 days. During this period, the rats were provided with a 12% casein diet or the formula diet which was low in aromatic amino acids and rich in branched chain amino acids. The formula diet was prepared using pork meat oligopeptides as the principal nitrogen source. The hepatitic rats given the formula diet had lower plasma GOT and GPT concentrations. Additionally, the fischer ratio of the plasma was significantly lower in those rats. However, there was no significant difference in the plasma insulin-like growth factor-I concentration before and after acid-ethanol extraction among groups. These results suggest that the formula diet was better for the animals than the casein diet. Furthermore, these findings suggest that pork meat oligopeptides are an excellent material for preparation of formula diets for patients suffering from hepatitis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.695-700
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• 2013

Background: Mutations affecting the epidermal growth factor receptor (EGFR) are good predictors of clinical efficacy of EGFR tyrosine kinase inhibitors (TKI) in patients with non-small cell lung cancer. Serum carcinoembryonic antigen (CEA) levels are also regarded as predictive for the efficacy of EGFR-TKI and EGFR gene mutations. This study analyzed the association between EGFR gene mutations and clinical features, including serum tumor marker levels in lung adenocarcinomas patients. Patients and Methods: A total of 70 lung adenocarcinoma patients with complete clinical data and pathological specimens were investigated. EGFR gene mutations at exons 19 and 21 were assessed. Serum tumor markers were detected by protein chip-chemiluminescence at the corresponding time, and correlations were analyzed. Results: Mutations of the EGFR gene were detected in 27 of the 70 patients and the serum CEA and CA242 concentrations were found to be significantly associated with the incidence of EGFR gene mutations (P<0.05). The AUCs for CEA and CA242 were 0.724 (95% CI: 0.598~0.850, P<0.05) and 0.769 (95% CI: 0.523~0.800, P<0.05) respectively. Conclusions: Serum CEA and CA242 levels are associated with mutations of the EGFR gene in patients with lung adenocarcinomas.