• Title/Summary/Keyword: vascular endothelial cell growth factor (VEGF)

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Characterization of EST Gene in the Bovine Corpus Luteum during the Estrous Cycle

  • Lee, Eunyoung;Kim, Sang Hwan;Kim, Byung-Gak;Yoon, Jong Taek
    • Development and Reproduction
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    • v.19 no.4
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    • pp.227-234
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    • 2015
  • The objective of this study was to investigate the expression of bovine luteum expressed sequence tags (ESTs), vascular endothelial growth factor (VEGF), and tumor necrosis factor receptor 1 (TNFR1) and the presence of functional ESTs in the bovine corpus luteum (CL) during different stages of the estrus cycle. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a difference in the expression of ESTs during the CL stage. Concentration of ESTs in the CL tissue increased significantly from the mid-luteal stage and decreased thereafter. RT-PCR analysis showed higher levels of the EST genes in the CL of the mid-luteal stage than in other stages, and the same level of expression of VEGF. Immunohistochemistry analysis of the tissue from CL formation to regression showed low cytosol and aggregation of the nucleus. And activity caspase 3 (apoptosis detector) was most strongly detected in the CL1 stage of bovine. During the estrous cycle, the cytosol was magnified and differentiation of the nucleus was clearly manifested. The ESTs affected the CL, and the relationship between VEGF and TNFR1 played a pivotal role for CL development and activation, dependent on the stage of CL. These results suggest local production of ESTs, the presence of functional ESTs in the bovine CL, and that ESTs play a role in regulating the function of cell death in bovine CL.

Mycoplasma pneumoniae-induced production of proasthmatic mediators in airway epithelium (인체 기관지 상피세포에서 Mycoplasma pneumoniae 감염에 의한 천식 매개물질의 발현)

  • Kim, Kyung Won;Lee, Byung Chul;Lee, Kyung Eun;Kim, Eun Soo;Song, Tae Won;Park, Mi Yeoun;Sohn, Myung Hyun;Kim, Kyu-Earn
    • Clinical and Experimental Pediatrics
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    • v.49 no.9
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    • pp.977-982
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    • 2006
  • Purpose : There has been an increasing amount of literature concerning the association between Mycoplasma pneumoniae and asthma pathogenesis. Interleukin(IL)-6 stimulates the differentiation of monocytes, and can promote Th2 differentiation and simultaneously inhibit Th1 polarization. IL-8 is a potent chemoattractant and, it has been suggested, has a role in asthma pathogenesis. Nitric oxide (NO) synthesized by airway epithelium may be important in the regulation of airway inflammation and reactivity. Vascular endothelial growth factor(VEGF) has been reported to be a mediator of airway remodeling in asthma. We investigated the effects of M. pneumoniae on IL-6, IL-8, NO and VEGF production in human respiratory epithelial cells. Methods : A549 cells were cultured and inoculated with M. pneumoniae at a dose of 20 cfu/cell. After infection, the presence of M. pneumoniae in epithelial cell cultures was monitored by immunofluorescence and confirmed by polymerase chain reaction(PCR) detection. IL-6, IL-8 and VEGF were determined by an enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. NO was measured using the standard Griess reaction. Results : In A549 cells, M. pneumoniaeinduced IL-6, IL-8, NO and VEGF release in time-dependent manners. It also induced mRNA expression of IL-6, IL-8 and VEGF in similar manners. Conclusion : These observations suggest that M. pneumoniae might have a role in the pathogenesis of the allergic inflammation of bronchial asthma.

Cripto Enhances Proliferation and Survival of Mesenchymal Stem Cells by Up-Regulating JAK2/STAT3 Pathway in a GRP78-Dependent Manner

  • Yun, SeungPil;Yun, Chul Won;Lee, Jun Hee;Kim, SangMin;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.464-473
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    • 2018
  • Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1. Notably, treatment with an anti-GRP78 antibody blocked these effects. In addition, pretreatment with STAT3 short interfering RNA (siRNA) inhibited the increase in p-JAK2, c-Myc, cyclin D1, and BCL3 levels caused by Cripto and attenuated the pro-survival action of Cripto on MSCs. We also found that incubation with Cripto protected MSCs from apoptosis caused by hypoxia or $H_2O_2$ exposure, and the level of caspase-3 decreased by the Cripto-induced expression of B-cell lymphoma 3-encoded protein (BCL3). These effects were sensitive to down-regulation of BCL3 expression by BCL3 siRNA. Finally, we showed that Cripto enhanced expression levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). In summary, our results demonstrated that Cripto activated a novel biochemical cascade that potentiated MSC proliferation and survival. This cascade relied on phosphorylation of JAK2 and STAT3 and was regulated by GRP78. Our findings may facilitate clinical applications of MSCs, as these cells may benefit from positive effects of Cripto on their survival and biological properties.

Anti-inflammatory effect of Samultang in human mast cell line HMC-1

  • Choi In-Young;Kim Su-Jin;Kang Tae-Hee;Lee Byung-Hee;Lee Joon-Ho;Lee Ju-Young;Kim Hyung-Min;Hong Seung-Heon;Um Jae-Young
    • Advances in Traditional Medicine
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    • v.6 no.3
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    • pp.237-244
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    • 2006
  • Samultang has been believed for prevention and remedy various blood diseases such as menstrual irregularity, anemia, and metrorrhagia. However, the mechanism that accounts for anti-inflammatory effects of the Samultang is still not fully understood. This study was designed to evaluate whether and how the Samultang could modulate the production of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 treated-human mast cell line, HMC-1. Samultang inhibited the production of tumor necrosis factor $(TNF)-\alpha$, interleukin (IL)-6, granulocyte macrophage colony stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in HMC-1. Maximal inhibition rate of $TNF-\alpha$, IL-6, GM-CSF, and VEGF by 0.1 mg/ml Samultang was about $70.73{\pm}3.0%,\;51.49{\pm}4.14%,\;54.03{\pm}2.09%$, and $47.95{\pm}7.86%$, respectively. Samultang partially blocked PMA plus A23187-induced cyclooxygenase (COX)-2 expression. In addition, Samultang inhibited activation of nuclear factor (NF)-kB, and extracellular signal-regulated kinase (ERK) activation. These results suggest that anti-inflammatory effect of Samulatng may be mediated by the suppression of cytokine production and COX-2 activation via down-regulation of NF-kB and ERK activation.

A STUDY ON THE EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN TENS10N SIDE OF RAT MOLAR PERIODONTAL LIGAMENT FOLLOWING EXPERIMENTAL TOOTH MOVEMENT (백서 구치의 실험적 치아이동시 견인측 치근막에서 혈관성장인자의 발현에 관한 연구)

  • Lim, Yong-Kyu;Shin, Choon-Shik;Lee, Dong-Ryul
    • The korean journal of orthodontics
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    • v.31 no.1 s.84
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    • pp.121-136
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    • 2001
  • This study was performed to analyse the expression of VEGF and it's receptor(VEGFR) in the tension side of the periodontal ligament following orthodontic tooth movement. Upper first molars of Sprague-Dawley rats were moved medially using closed coil spring for 1, 2, 24 hours and 3, 7, 14 days. H&E staining, immunohistochemical staining and in situ hybridization methods were used to analyse the change of the expression of VEGF and VEGFR. The results from this study were as follows : 1. Following tensional force, periodontal ligament showed elongation of fibers, compression and congestion of vessels and regional hemorrhage. These tissue changes were recovered within 3 days of force application. New bone formation was seen after 3 days of force application and continued for the remaining experimental periods. 2. Following tensional force, VEGF and VEGF mRNA expression was increased in the periodontal ligament cells, osteoblasts and cementoblasts. This change was followed by increased vasculature in the periodontal ligament. 3. After 3 days of tensional force, VEGF and VEGF mRNA expression was confined mainly to the osteopaths and the periodontal ligament cells adjacent to the alveolar bone. After 2 weeks of force application, VEGF and VEGF mRNA expression was reduced to the level of control sample. 4. VEGFRs(Flt-1, Flk-1) showed similar expression pattern and it's expression was mainly seen in the endothelial cells and osteoblasts. Following tensional force VEGFR expression was increased in the endothelial cells and osteoblasts. In conclusion, in the tension side of the penodontal ligament, ligament cells, osteoblast and cementoblast showed increased expression of VEGF & VEGF mRNA. It preceded the increase of vasculature and new bone formation. The increased expression of VEGF mRNA in cementoblast may induce periodontal vessels, which distribute mainly the bone side half of periodontal ligament, grow in the direction of tensional force. Increased expression of VEGFR & VEGFR mRNA not only in endothelial cell but in osteoblast, osteocyte and periodontal cells showed VEGF acts not only in paracrine manner but in autocrine one.

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3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

  • Kim, Young Eun;Choi, Hyung Chul;Lee, In-Chul;Yuk, Dong Yeon;Lee, Hyosung;Choi, Bu Young
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.572-580
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    • 2016
  • 3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of ${\beta}$-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of $WNT/{\beta}$-catenin and STAT signaling.

The Effect of Treadmill Exercise on Ischemic Neuronal Injury in the Stroke Animal Model: Potentiation of Cerebral Vascular Integrity (중풍 동물 모델에서의 트레드밀 운동이 허혈성 신경손상에 미치는 효과: 뇌혈관 통합성 강화)

  • Kang, Kyoung-Ah;Seong, Ho-Hyun;Jin, Han-Byeol;Park, Jong-Min;Lee, Jong-Min;Jeon, Jae-Yong;Kim, Youn-Jung
    • Journal of Korean Academy of Nursing
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    • v.41 no.2
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    • pp.197-203
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    • 2011
  • Purpose: This study was done to identify whether pre-conditioning exercise has neuroprotective effects against cerebral ischemia, through enhance brain microvascular integrity. Methods: Adult male Sprague-Dawley rats were randomly divided into four groups: 1) Normal (n=10); 2) Exercise (n=10); 3) Middle cerebral artery occlusion (MCAo), n=10); 4) Exercise+MCAo (n= 10). Both exercise groups ran on a treadmill at a speed of 15 m/min, 30 min/day for 4 weeks, then, MCAo was performed for 90 min. Brain infarction was measured by Nissl staining. Examination of the remaining neuronal cell after MCAo, and microvascular protein expression on the motor cortex, showed the expression of Neuronal Nuclei (NeuN), Vascular endothelial growth factor (VEGF) & laminin. Results: After 48 hr of MCAo, the infarct volume was significantly reduced in the Ex+MCAo group ($15.6{\pm}2.7%$) compared to the MCAo group ($44.9{\pm}3.8%$) (p<.05), and many neuronal cells were detected in the Ex+ MCAo group ($70.8{\pm}3.9%$) compared to the MCAo group ($43.4{\pm}5.1%$) (p<.05). The immunoreactivity of laminin, as a marker of microvessels and Vascular endothelial growth factor (VEGF) were intensively increased in the Ex+MCAo group compared to the MCAo group. Conclusion: These findings suggest that the neuroprotective effects of exercise pre-conditioning reduce ischemic brain injury through strengthening the microvascular integrity after cerebral ischemia.

Experimental Studies on the Hair Growth Activity of Drynariae Rhizoma Extracts in C57BL/6N Mice (C57BL/6N 생쥐에서 골쇄보(骨碎補) 추출물을 이용한 발모(發毛)효과에 대한 실험적 연구)

  • Jung, Suk-Young;Jung, Il-Kook;Kim, Dae-Keun;Jo, Han-Young;Jung, Han-Sol;Lee, Chang-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.2
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    • pp.453-461
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    • 2007
  • Drynariae Rhizoma has been used for promotes mending of the sinews and bone, tonifies the kidney for such symptoms as weak low back and knees, and stimulates the growth of hair as a tinctute for alopecia in oriental medicine. This experiment examined the effect of an acetone extracts of Drynariae Rhizomas(GSB-1), its EtoAc fraction(GB-2) and n-buOH fraction(GSB-3), on hair growth activity of the C57BL/6L mice after topical application to skin. First, We examined on hair growth activity of extracts of Drynariae Rhizomas compare to control and 1 % minoxidil groups. Second, We investigated on the number of hair follicle and mast cells after topical application of extracts of the Drynariae Rhizomas to skin for 16 day. Third, We investigated immunoreactive density of vascular endothelial growth factor(VEGF), protein kinase C-${\alpha}$(PKC-${\alpha}$) and stem(mast) cell factor(SCF) in skin of C57BL/6N mice by immunohistochemical methods. The results were as follows : Hair growth effect of acetone extracts of Drynariae Rhizomas, its EtoAc fraction and n-BuOH fraction was observed in 98 %, 96 % and 60 % in hair removed skin area in 16 day respectively, Immunoreactive density of VEGF in skin of GSB-1 group was weakly stained compare to control group in 10 day, But GSB-2 and GSB-3 groups were mildy stained in bulge and root sheath of skin. Immunolocalization of SCF antigens was observed weakly stained density in epidermis, bulge, stem cells and dermal papilla of control gruop. but in experimental group, immunoreactivity of SCF antigens was observed mildly stained density in bulge, epidermis and root sheath of GSB-1 gruop, heavily stained density in epidermis, bulge and root sheath of GSB-2 and GSB-3 groups to the hair removal skin of C57BL/6N mice on day 10. These experiment suggest that acetone extracts of Drynariae Rhizomas and its EtoAc fraction may be used for topical treatment of alopecia areata.

Regulatory Effect of Inflammatory Cytokines Secretion and Hypoxia-inducible $Factor-1{\alpha}$ Activation by Panax ginseng (인삼의 염증성 사이토카인 분비 및 저산소 유도인자-1${\alpha}$ 활성화 조절 효과)

  • Zo, Chul-Won;Lee, Seung-Hee;Kim, Dong-Woung;Lee, Seong-Kyun;Song, Bong-Keun
    • The Journal of Internal Korean Medicine
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    • v.27 no.4
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    • pp.864-878
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    • 2006
  • Purpose : Panax ginseng(PG) is considered to have salutary effects and stimulant actions on physical capacity. However, the effects of PG on the inflammatory cytokine secretion and hypoxia condition are still not understood. This study wasto elucidate the effect of PG on inflammatory cytokine secretion such as interleukin (IL)-1, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$. Also, the effects on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) were measured. Methods : The water extract of PG was administrated to HMC-1 cells before phorbol myristate acetate (PMA)+A23187 treatment. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, GM-CSF, and VEGF secretion were measured by a modified enzyme-linked immunosorbent assay (ELISA). HIF-1 activation was measured by transcription factor enzyme-linked immunoassay (TF-EIA) Results : PG significantly decreased secretion of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, and GM-CSF in PMA+A23187-induced HMC-1 cells. VEGF secretion was not changed but HIF-1 activation was decreased by the treatment of PG. Conclusions : PG inhibited the secretion of inflammatory cytokines, which impliesPG might contribute to treatment of mast cell-mediated inflammatory disease. Also, PG inhibited PMA+A23187-induced $HIF -1{\alpha}activation}$ and DNA-binding activity for HIF-1. Therefore, these data demonstrate that PG modulates inflammatory cytokines through inhibition of $HIF-1{\alpha}activation}$ activation.

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Decontamination methods to restore the biocompatibility of contaminated titanium surfaces

  • Jin, Seong-Ho;Lee, Eun-Mi;Park, Jun-Beom;Kim, Kack-Kyun;Ko, Youngkyung
    • Journal of Periodontal and Implant Science
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    • v.49 no.3
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    • pp.193-204
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    • 2019
  • Purpose: The reaction of cells to a titanium implant depends on the surface characteristics of the implant which are affected by decontamination. The aim of this study was to evaluate the cytocompatibility of titanium disks treated with various decontamination methods, using salivary bacterial contamination with dental pellicle formation as an in vitro model. Methods: Sand-blasted and acid-etched (SA) titanium disks were used. Three control groups (pristine SA disks [SA group]; salivary pellicle-coated SA disks [pellicle group]; and biofilm-coated, untreated SA disks [NT group]) were not subjected to any decontamination treatments. Decontamination of the biofilm-coated disks was performed by 14 methods, including ultrasonic instruments, rotating instruments, an air-powder abrasive system, a laser, and chemical agents. MG63 cells were cultured in the presence of the treated disks. Cell proliferation assays were performed on days 2 and 5 of cell culture, and cell morphology was analyzed by immunofluorescence and scanning electron microscopy (SEM). A vascular endothelial growth factor (VEGF) assay was performed on day 5 of culture. Results: The cell proliferation assay revealed that all decontaminated disks, except for the 2 groups treated using a plastic tip, showed significantly less cell proliferation than the SA group. The immunofluorescence and SEM analyses revealed that most groups showed comparable cell density, with the exception of the NT group, in which the cell density was lower and bacterial residue was observed. Furthermore, the cells grown with tetracycline-treated titanium disks showed significantly lower VEGF production than those in the SA group. Conclusions: None of the decontamination methods resulted in cytocompatibility similar to that of pristine SA titanium. However, many methods caused improvement in the biocompatibility of the titanium disks in comparison with the biofilm-coated, untreated titanium disks. This suggests that decontamination is indispensable for the treatment of peri-implantitis, even if the original biocompatibility cannot be restored.