• 제목/요약/키워드: Vascular Remodeling

검색결과 68건 처리시간 0.027초

인간 폐섬유아세포에서 TGF-β 자극에 의한 VEGF 분비 (Transforming growth factor-β promoted vascular endothelial growth factor release by human lung fibroblasts)

  • 박상욱;신주화;심재원;김덕수;정혜림;박문수;심정연
    • Clinical and Experimental Pediatrics
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    • 제51권8호
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    • pp.879-885
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    • 2008
  • 목 적 : 폐섬유아세포는 예전에는 기도의 구조적 세포로만 알려져 왔으나, 최근에는 천식에서 기관지 운동의 톤을 조절할 뿐만 아니라 기도의 면역조절과 기도 개형에서 중요한 역할을 하는 것으로 밝혀지고 있다. VEGF는 혈관 내피세포에서 강력한 작용을 하는 다기능적 사이토카인으로서, 상피내 세포의 세포분열을 유도하고, 상피세포의 투과도를 증가시키며, 상피세포의 이동을 향상시키는 역할을 하는 것으로 알려져 있다. TARC는 Th2 세포의 선택적 이동을 유도하는 케모카인으로 알려져 있다. 본 연구에서는 PDGF와 TGF-${\beta}$로 자극시킨 인간 폐섬유아세포에서 VEGF와 TARC가 생성되는지와 dexamethasone이 폐섬유아세포에서 VEGF의 분비를 억제하는지를 알아보고자 하였다. 또한 폐섬유아세포와 기관지 평활근 세포와 함께 배양했을 때 VEGF 생성에 미치는 효과를 단독배양 시와 비교하였다. 방 법 : 폐섬유아세포와 인간 기관지 평활근세포를 각각 혹은 함께 배양한 뒤 48시간동안 무혈청 배지에서 성장을 정지시킨 후 TGF-${\beta}$ (10 ng/mL)와 PDGF (20 ng/mL)로 자극하였다. 자극 후의 세포 증식 반응과 배양액 상층액의 VEGF, TARC 농도를 측정하여 dexamethasone ($10^{-6}M$)으로 전처치 후 자극한 것과 비교하였다. 결 과 : PDGF와 TGF-${\beta}$로 자극하였을 경우 폐섬유아세포에서 VEGF 분비가 의미있게 증가하였고, 특히 PDGF와 TGF-${\beta}$로 함께 자극하였을 경우 더욱 의미있는 상승을 보였다. Dexamethasone은 폐섬유아세포의 VEGF 분비를 PDGF로 자극한 경우와 PDGF, TGF-${\beta}$ 같이 자극한 경우 모두에서 억제하였다. 인간 기관지 평활근 세포와 폐섬유아세포를 혼합 배양했을 때 VEGF 분비에는 상승적인 효과가 없었다. Dexamethasone은 폐섬유아세포 증식을 억제시키지 않았다. 폐섬유아세포를 PDGF와 TGF-${\beta}$로 자극했을 때 TARC는 분비되지 않았다. 결 론 : 폐섬유아세포는 VEGF 분비를 통해 기도 개형에 관여하며, 기관지 평활근 세포와 함께 배양해도 VEGF 분비에 상승 효과는 없다. Dexamethasone은 VEGF 분비를 억제하였으나 폐섬유아세포의 증식을 억제하지는 못하였다.

저칼슘식이 투여와 방사선조사가 임프란트의 골유착에 미치는 영향에 관한 실험적 연구 (Osseointegration of Implants in Rabbit Bone with a Low Calcium Diet and Irradition)

  • 김소정;황의환;이상래
    • Imaging Science in Dentistry
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    • 제30권1호
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    • pp.33-48
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    • 2000
  • Purpose : To investigate osseointergration of titanium implants into the tibia of rabbits, which were fed a low calcium diet and irradiated. Materials and Methods : To prepare the experimental model, control group was fed a normal diet and experimental group was fed a low calcium diet for 4 weeks. And then, titanium implants were inserted into the tibia of each rabbit. Experimental group was subdivided into two groups; low calcium diet/non-irradiation group and low calcium diet/irradiation group. The low calcium diet/irradiation group was irradiated with a single absorbed dose of 15 Gy at the 5th postoperative day. At 12, 19, 33, 47, and 61 days after implantation (1, 2, 4, 6, and 8 weeks after irradiation), the bone formation in the bone-implant interface area was examined by light microscopy and fluorescent microscopy. Results and Conclusions: 1. In the control group, there began to form woven bone in the bone-implant interface area at 12 days after implantation. As the experimental time was going on, the amount of bone which was in contact with the implant was increased. 2. In the low calcium diet/non-irradiation group, there began to form woven bone in the bone-implant interface area at 19 days after implantation. Although the amount of bone which was in contact with the implant was increased as the experimental time was going on, the extent of increased bone was weak as compared with control group. 3. In the low calcium diet/irradiation group, there began to form woven bone incompletely in the bone-implant interface area at 19 days after implantation, but there were vascular connective tissues in the bone-implant interface area over the entire experimental period. 4. In the control group and low calcium diet/non-irradiation group, bone labeling bands were observed at 33 days after implantation, which suggests that the bone formation and remodeling was in process, but interstitial bone remodeling was not observed in the low calcium diet/irradiation group.

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인간의 갑상선 결절성 과증식증과 유두상 암종에서의 Endothelial Nitric Oxide의 발현 (Expression of Endothelial Nitric Oxide Synthase in Benign Nodular Hyperplasia and Papillary Carcinoma of Human Thyroid Gland)

  • 김영모;조정일;김용재;양태용;김대형;박창신;한창준
    • 대한두경부종양학회지
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    • 제17권2호
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    • pp.155-161
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    • 2001
  • Background and Objectives: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. This reaction is catalyzed by nitric oxide synthase (NOS). NO is an important bioactive agent and a signalling molecule that mediates a variety of biologic actions such as vasodilation, neurotransmission, host defense, and iron metabolism but increased NO production may also contribute to the pathogenesis of a various of disorders, including cancer. Before now, the role of NO in thyroid gland is still investigated and it was supposed that NO mediate the angiogenesis in tumor growth. Others journal and works identified the expression of iNOS that involve by neutrophil and eNOS that involve in part in the vascular remodeling and to understand the role of NO in human thyroid gland. But authors revealed only eNOS in thyroid neoplasm. iNOS was identifed by inflammation in fault. Materials and Methods: Western blot analysis was performed, using a polyclonal antibody against eNOS (Rabbit polyclonal IgG). Using the same antibody, the distribution of eNOS was examined in 15 formalin-fixed paraffin embedded samples by immunohistochemistry. By NADPH consumption rate, NOS activity was estimated at nodular hyperplasia. Results: Western blot analysis exhibited that eNOS was significantly elevated in thyroid papillary carcinoma, compared to that in nodular hyperplasia and normal tissue. Immunohistochemistry showed that the immunoreacitivity was present more significantly in thyroid follicular epithelial cell layer than vascular endothelial cell. NOS activity increased in nodular hyperplasia. Conclusions: Thyroid papillary cancer without neutrophil invasion expressed only eNOS. The endothelial localization of eNOS may play an important role in pathogenensis of human thyroid nodular hyperplasia and the follicular localization of thyroid papillary carcinomas.

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허혈성 심혈관 질환의 치료제로서 혈관내피전구세포(EPC)의 가능성에 대한 고찰 (The Potential Therapeutic Effects of Endothelial Progenitor Cells in Ischemic Cardiovascular Disease)

  • 김다연;김보민;김소정;최진희;권상모
    • 생명과학회지
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    • 제30권7호
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    • pp.651-659
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    • 2020
  • 허혈성 심혈관질환은 전 세계적으로 치사율이 높은 질병 중 하나이다. 이를 치료하기 위해 수술적 방법이 시행되고 있으나, 손상된 심근조직 회복의 어려움과 수술 후 부작용의 한계가 남아있다. 이러한 한계점을 극복하기 위해, 최근 줄기세포를 기반으로 한 심혈관질환의 세포치료제가 각광받고 있는데 그 중에서도 특히 혈관내피전구세포(EPC)는 높은 증식능과 분화능을 기반으로 손상된 혈관을 재생하고, 주변 조직의 재생을 돕는다는 장점이 있다. 또, EPC는 임상적으로 안전하며, 환자의 심근 기능을 회복시켜주기에 잠재적인 심혈관질환 치료제로서의 가능성이 대두되었다. 하지만, 환자 유래 EPC를 이용한 치료법은, 고령, 흡연 여부, 기저질환 등의 이유로 환자의 EPC 기능이 저하되어 있어, 그 치료 효능을 기대하기 어렵다. 따라서, 최근에는 세포 프라이밍 기법, 오가노이드 배양법과 같이 EPC의 생리학적 활성도를 올리는 체외 배양법의 개발과 3D 바이오프린팅 기법을 이용한 EPC의 이식 효율을 높여 치료 효능을 개선시킬 수 있는 새로운 접근법이 연구되고 있다. 본 연구에서는 EPC의 특징과 세포치료제로서의 임상적용 가능성에 대해 살펴보고자 한다.

Loss of ARID1A Expression in Gastric Cancer: Correlation with Mismatch Repair Deficiency and Clinicopathologic Features

  • Kim, Kyung-Ju;Jung, Hae Yoen;Oh, Mee-Hye;Cho, Hyundeuk;Lee, Ji-Hye;Lee, Hyun Ju;Jang, Si-Hyong;Lee, Moon Soo
    • Journal of Gastric Cancer
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    • 제15권3호
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    • pp.201-208
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    • 2015
  • Purpose: The AT-rich interactive domain 1A (ARID1A ) gene encodes BRG1-associated factor 250a, a component of the SWItch/Sucrose NonFermentable chromatin remodeling complex, which is considered a tumor suppressor in many tumors. We aimed to investigate the prognostic significance of ARID1A expression in gastric cancers and explore its relationship with clinicopathologic parameters such as mismatch repair protein expression. Materials and Methods: Four tissue microarrays were constructed from 191 resected specimens obtained at Soonchunhyang University Cheonan Hospital from 2006 to 2008. Nuclear expression of ARID1A was semiquantitatively assessed and binarized into retained and lost expression. Results: Loss of ARID1A expression was observed in 62 cases (32.5%). This was associated with more frequent vascular invasion (P=0.019) and location in the upper third of the stomach (P=0.001), and trended toward more poorly differentiated subtypes (P=0.054). ARID1A loss was significantly associated with the mismatch repair-deficient phenotype (P=0.003). ARID1A loss showed a statistically significant correlation with loss of MLH1 (P=0.001) but not MSH2 expression (P=1.000). Kaplan-Meier survival analysis showed no statistically significant difference in overall survival; however, patients with retained ARID1A expression tended to have better overall survival than those with loss of ARID1A expression (P=0.053). In both mismatch repair-deficient and mismatch repair-proficient groups, survival analysis showed no differences related to ARID1A expression status. Conclusions: Our results demonstrated that loss of ARID1A expression is closely associated with the mismatch repair-deficient phenotype, especially in sporadic microsatellite instability-high gastric cancers.

정맥기형 환자에 있어서의 유전자 발현 차이 (Difference of Gene Expression in Venous Malformation)

  • 김택균;오은정;조병채;정호윤
    • Archives of Plastic Surgery
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    • 제34권6호
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    • pp.671-678
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    • 2007
  • Purpose: Venous malformation(VM) which often causes pain and discomfort is the most common type of vascular malformations. Although it is presented with disfigured appearance and associated soft tissue or skeletal hypertrophy, the molecular bases of VMs are poorly understood. Differentially expressed genes(DEGs) of VMs were investigated to illuminate the molecular mechanism of the disease entity. Methods: Gene expressions of VM patients' subcutaneous tissue were studied in comparison with normal persons' by $GeneFishing^{TM}$ technique using the annealing control primers (ACPs) to identify DEGs. Candidate genes were sequenced and screened by basic local alignment search tool (BLAST) afterwards. Results: Among seventy DEGs identified, forty DEGs which had shown significantly different expression pattern were sequenced. Twenty eight out of 40 were up-regulated while 12 were down-regulated. BLAST searches revealed that 37 were known genes and 3 were unknown genes. Many genes were involved in the differentiation and remodeling of smooth muscle cells, opposed to the previous hypothesis that a lot of angiogenetic genes would be involved. Furthermore, several transcription factors and related genes, as well as cell signaling and metabolism regulators, were up regulated. Conclusion: It suggests that analysis of DEGs in VMs provide basic knowledge about its pathophysiology. and new therapeutic approaches.

치근단질환에서 형질전환성장인자-β와 기질금속함유단백분해효소 발현에 관한 연구 (A STUDY ON THE EXPRESSION OF TRANSFORMING GRO WITH FACTOR-β AND MATRIX METALLOPROTEINASE-1 IN PERIAPICAL LESION)

  • 지정호;이수종
    • Restorative Dentistry and Endodontics
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    • 제24권1호
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    • pp.200-211
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    • 1999
  • The periapical response to injury is a complex interaction of inflammatory, immune, neural, vascular and synthetic activity. TGF-${\beta}$ is a potent modulator of proliferation and differentiation in various tissue, seems to lead to an increase in extracellular matrix. MMP are a family of proteolytic enzyme that mediate the degradation of extracellular matric macromolecules, but little is known about theirs possible role in periapical tissue. The purpose of this study is to investigate the differential expression of TGF-${\beta}$ and MMP-1 in tooth follicle, periapical abscess, granuloma and cyst. The expression of TGF-${\beta}$ and MMP-1 in Periapical tissue was evaluated by immunohistochemical staining and Western blot analysis. Correlationship among the periapical lesions were stastically analyzed. The degree of MMP-1 expression in periapical abscess was higher than in any other periapical lesion, and stastically significant. TGF-${\beta}$ expression is the prominent in granuloma than other periapical lesion, which was stastically significant. The increased expression of MMP and TGF-${\beta}$ was not co-related with inflammatory cell infiltration degree of the periapical cyst. The expression degree of MMP and TGF-${\beta}$ was not co-related with periapical abscess and cyst, but expression of MMP and TGF-${\beta}$ showed strong positive co-relationship with periapical granuloma, which was stastically significant. TGF-${\beta}$ expression by Western blot analysis was prominent in granuloma and cyst, and similar to the results by imunohistochemistry. MMP-1 expression is less than TGF-${\beta}$, but there is not extreme difference between periapical lesion. These results suggest that TGF-${\beta}$ and MMP may be involved in tissue remodeling and has an important role in progress or mediation of periapical lesions.

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흰쥐의 급성 위점막 손상에서 황연탕(黃蓮湯)이 apoptosis 관련단백질 및 성장인자 발현에 미치는 영향 (The Protective Effects of $Hwangyeon-tang$ on Acute Gastric Ulcer induced by HCl/EtOH solution in Rats)

  • 김범회
    • 대한예방한의학회지
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    • 제16권1호
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    • pp.57-70
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    • 2012
  • The apoptotic process of gastric mucosa triggered by induction of proapoptotic gene expression, such as Bax. Stress-inducing factors may affect Bcl-2/Bax ratio and thus the rate of apoptosis through modulation of the expression of both proteins depending upon the experimental model. TGF-${\beta}$ is believed to be essential in wound healing for regulation of cell growth and differentiation and is known to be involved in tissue repair and remodeling. The polypeptide growth factors, such as vascular endothelial growth factor(VEGF), regulate essential cell functions involved in tissue healing including cell proliferation, migration, and differentiation. The purpose of this study was to investigate whether the oral administration of $Hwangyeon-tang$ (HYT) would have protect effects on gastric ulcer in rat. Sprague-Dawley rats (n=40) were randomly divided into 4 groups ; Normal, Saline, Cimetidine and HYT group. The saline, cimetidine and HYT extract were orally administrated to each group and gastric ulcer was induced with HCl/EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In Results, the wound healing of gastric ulcer was promoted by HYT and the significant alterations of BAX/Bcl-2, TGF-${\beta}1$ and VEGF proteins in gastric mucosa were observed. These results suggest that Fritillaria ussuriensis extract promotes wound healing and has protective effects on gastric ulcer in rats.

저출력 레이져 자극이 근육세포의 증식 및 유전자 발현에 미치는 효과 (Effect of Low-Energy Laser Irradiation on the Proliferation and Gene Expression of Myoblast Cells)

  • 곽지현;전옥희;강동연;유현희;김경환;정병조;김지현
    • 대한의용생체공학회:의공학회지
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    • 제31권1호
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    • pp.81-86
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    • 2010
  • Laser irradiation is known to affect various tissues such as skin, bone, nerve, and skeletal muscle. Laser irradiation promotes ATP synthesis, facilitates wound healing, and stimulates cell proliferation and angiogenesis. In skeletal muscle, laser irradiation is related to the proliferation of skeletal muscle satellite cells. Normal skeletal muscle contains remodeling capacity from myogenic cells that are derived from mononuclear satellite cells. Their processes are activated by the expression of genes related with myogenesis such as muscle-specific transcription factors (MyoD and Myf5) and VEGF (vascular endothelial growth factor). In this study, we hypothesized that laser irradiation would enhance and regulate muscle cell proliferation and regeneration through modulation of the gene expressions related with the differentiation of skeletal muscle satellite cells. $C_2C_{12}$ myoblastic cells were exposed to continuous/non-continuous laser irradiation (660nm/808nm) for 10 minutes daily for either 1 day or 5 days. After laser irradiation, cell proliferation and gene expression (MyoD, Myf5, VEGF) were quantified. Continuous 660nm laser irradiation significantly increased cell proliferation and gene expression compared to control, continuous 808nm laser irradiation, and non-continuous 660nm laser irradiation groups. These results indicate that continuous 660nm laser irradiation can be applied to the treatment and regeneration of skeletal muscle tissue.

Suppression of Inflammation, Osteoclastogenesis and Bone Loss by PZRAS Extract

  • Li, Liang;Park, Young-Ran;Shrestha, Saroj Kumar;Cho, Hyoung-Kwon;Soh, Yunjo
    • Journal of Microbiology and Biotechnology
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    • 제30권10호
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    • pp.1543-1551
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    • 2020
  • Panax ginseng has a wide range of activities including a neuroprotective effect, skin protective effects, enhanced DNA repairing, anti-diabetic activity, and protective effects against vascular inflammation. In the present study, we sought to discover the inhibitory effects of a mixture of natural products containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling, as neither the effects of a mixture containing Panax ginseng extract, nor its molecular mechanism on bone inflammation, have been clarified yet. PZRAS upregulated the levels of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in LPS-treated RAW264.7 cells. Moreover, treatment with PZRAS decreased the production of IL-1β and TNF-α. PZRAS also inhibited osteoclast differentiation through inhibiting osteoclastspecific genes like MMP-2, 9, cathepsin K, and TRAP in RANKL-treated RAW264.7 cells. Additionally, PZRAS has inhibitory functions on the RANKL-stimulated activation of ERK and JNK, which lead to a decrease in the expression of NFATc1 and c-Fos. In an in vivo study, bone resorption induced by LPS was recovered by treatment with PZRAS in bone volume per tissue volume (BV/TV) compared to control. Furthermore, the ratio of eroded bone surface of femurs was significantly increased in LPS-treated mice compared to vehicle group, but this ratio was significantly reversed in PZRAS-treated mice. These results suggest that PZRAS could prevent or treat disorders with abnormal bone loss.