• Radiation Oncology Journal
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• 제28권1호
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• pp.32-38
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• 2010

목 적: 항암요법에 의한 부작용 중 방사선섬유증(radiation fibrosis)은 방사선치료 후 빈번하게 일어나지만 발생빈도 및 심각성에 비해 치료법이 제한적이다. 본 연구에서는 방사선섬유증의 기전 연구 및 치료제 개발을 위해 방사선섬유증 동물모델계를 확립하고자 하였다. 대상 및 방법: 마우스의 대퇴부에 20 Gy의 방사선을 1주 간격으로 2회 조사한 후 날짜 별로 육안적 평가와 haematoxylin & eosin (H&E) 및 Masson’s Trichrome 염색을 통한 조직학적 변화를 평가하였다. 연부조직 수축도를 평가하기 위하여 특별히 고안된 틀을 이용하여 양쪽 하지의 길이 차이를 측정하였고, transforming growth factor (TGF)-${\beta}$의 발현 정도를 면역조직염색 및 중합효소연쇄반응(polymerase chain reaction)을 통해 측정하였다. 결 과: 본 연구에서 20 Gy씩 2회의 방사선조사를 시행하고 14, 28, 42, 97일 후 양측 하지의 수축도를 비교한 결과 42일 이후에 유의한 길이 차이가 나타났고 조직검사 결과 방사선이 조사된 피부 및 연부조직에서 아교질(collagen)과 세포외바탕질(extracellular matrix) 섬유가 불규칙한 배열을 나타내었으며 근육섬유모세포(myofibroblast)의 증가가 관찰되었다. TGF-${\beta}$ 발현 정도를 면역염색으로 조사한 결과 시간이 지남에 따라 증가하였고, 중합효소연쇄반응상 mRNA 발현량도 대조군에 비해 유의하게 증가하였다. 결 론: BALB/c 마우스의 대퇴부에 20 Gy의 방사선을 2회 조사하였을 때 방사선섬유증과 관련된 주요 인자인 TGF-${\beta}$의 발현량이 증가하였을 뿐만 아니라 외관적으로도 뚜렷한 방사선섬유증이 관찰되어 앞으로의 연구를 위한 효과적인 동물모델계로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제29권9호
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• pp.1349-1360
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• 2019

Chronic exposure to ultraviolet (UV) radiation, regarded as a major cause of extrinsic aging or photoaging characterized by wrinkle formation and skin dehydration, exerts adverse effects on skin by causing the overproduction of reactive oxygen species. Agastache rugosa Kuntze, known as Korean mint, possesses a wide spectrum of biological properties including anti-oxidation, anti-inflammation, and anti-atherosclerosis. Previous studies have reported that A. rugosa protected human keratinocytes against UVB irradiation by restoring the anti-oxidant defense system. However, the anti-photoaging effect of A. rugosa extract (ARE) in animal models has not yet been evaluated. ARE was orally administered to hairless mice at doses of 100 or 250 mg/kg/day along with UVB exposure for 12 weeks. ARE histologically improved UVB-induced wrinkle formation, epidermal thickening, erythema, and hyperpigmentation. In addition, ARE recovered skin moisture by improving skin hydration and transepidermal water loss (TEWL). Along with this, ARE increased hyaluronic acid levels by upregulating HA synthase genes. ARE markedly increased the density of collagen and the amounts of hydroxypoline via two pathways. First, ARE significantly downregulated the mRNA expression of matrix metalloproteinases responsible for collagen degradation by inactivating the mitogen-activated protein kinase/activator protein 1 pathway. Second, ARE stimulated the transforming growth factor beta/Smad signaling, consequently raising the mRNA levels of collagen-related genes. In addition, ARE not only increased the mRNA expression of anti-oxidant enzymes but also decreased inflammatory cytokines by blocking the protein expression of nuclear factor kappa B. Collectively, our findings suggest that A. rugosa may be a potential preventive and therapeutic agent for photoaging.

• 생명과학회지
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• 제25권12호
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• pp.1425-1431
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• 2015

면역 시스템의 림프구는 B 림프구와 T 림프구 두 종류로 나눌 수 있다. B 림프구는 플라즈마 세포로 분화하여 항체를 생성하는 체액성 면역을 담당하며, T 림프구는 다른 세포나 세균을 죽이는 세포성 면역을 담당한다. 고전적으로 B 림프구와 T 림프구의 작용은 한 방향으로 이뤄졌다. T 림프구는 B 림프구의 분화를 촉진하고 면역글로불린종류의 전환을 조절한다. T 림프구가 부족한 경우 B 림프구의 부족을 초래함이 보고되어 있다. 그러나 최근에 역으로 B 림프구가 T 림프구의 분화와 활성을 조절할 수 있다는 보고가 있다. 예를 들어, B 림프구는 CD8+ T 림프구의 tolerance를 직접 조절할 수 있고, TGF-β의 분비를 통해 T 림프구의 anergy를 유도할 수 있다. 본 연구는 LPS에 의해 자극된 B 림프구가 수지상세포에서 IL-12의 분비를 억제하여 Th1 림프구의 분화를 억제할 수 있음을 보여준다. 이 억제는 B 림프구와 수지상세포의 직접적인 interaction에 의해 일어나는 것이 아니며 B 림프구가 수지상세포의 성숙을 조절하여 일어나는 것도 아니다. B 림프구에서 분비되는 soluble factor가 LPS에 의해 증가되는 수지상세포의 IL-12p35 transcription을 억제한다. 이 결과들은 B 림프구가 매개하는 새로운 면역억제 기전이 존재함을 보여준다. 이것은 고전적인 방향성을 가진 T 림프구에 의한 B 림프구 작용조절로 면역반응이 결정되는 것이 아니라 T 림프구와 B 림프구가 서로 작용을 하여 면역평형을 결정하는 기전이 존재함을 보여준다.

• BMB Reports
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• 제50권6호
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• pp.308-317
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• 2017

Bone morphogenetic protein type 2 receptor (BMPR2) is one of the transforming growth $factor-{\beta}$ ($TGF-{\beta}$) superfamily receptors, performing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2 consists of 1,038 amino acids, and contains functionally conserved extracellular, transmembrane, kinase, and C-terminal cytoplasmic domains. Bone morphogenetic proteins (BMPs) engage the tetrameric complex, composed of BMPR2 and its corresponding type 1 receptors, which initiates SMAD proteins-mediated signal transduction leading to the expression of target genes implicated in the development or differentiation of the embryo, organs and bones. In particular, genetic alterations of BMPR2 gene are associated with several clinical disorders, including representative pulmonary arterial hypertension, cancers, and metabolic diseases, thus demonstrating the physiological importance of BMPR2. In this mini review, we summarize recent findings regarding the molecular basis of BMPR2 functions in BMP signaling, and the versatile roles of BMPR2. In addition, various aspects of experimentally validated pathogenic mutations of BMPR2 and the linked human diseases will also be discussed, which are important in clinical settings for diagnostics and treatment.

• Journal of Acupuncture Research
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• 제20권3호
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• pp.1-14
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• 2003

Objective : The aim of the study was to investigate the preventive effect of Acanthopanax senticosus(AS) aqua-acupuncture into Sinsu(BL23) of the multiple low-does strepozotocin(STZ)-induced diabetic rats. Methods : The experimental animals were divided into 4 groups : normal group of rats, control group of multiple low-does STZ-induced diabetic rats, NSAA group with 0.4ml normal saline(NS) aqua-acupunctured subcutaneously into Sinsu in multiple low-does STZ-induced diabetic rats, and ASAA group with 0.4ml of 20% AS aqua-acupunctured subcutaneously into Sinsu in multiple low-does STZ-induced diabetic rats. Each of AS and NS aqua-acupuncture was done subcutaneously into both loci of Sinsu taking turns everyday for 3 weeks. Thereafter the levels of serum glucose, body weight, index of kidney hypertrophy, urine glucose, urinary albumin excretion, creatinine clearance, mesangial cell and TGF-${\beta}1$ expression in glomeruli and tubular cells were measured on the determined day. Conclusions : 1. Both ASAA and NSAA groups decreased the serum glucose levels in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group showed more significant decreases than NSAA group. 2. Both ASAA and NSAA groups prevented the development of diabetes in multiple low-dose STZ-induced diabetic rats as compared to the control group, and ASAA group prevented more markedly the development of diabetes than NSAA group. 3. Both ASAA and NSAA groups prevented the reduction of body weight in multiple low-dose STZ-induced diabetic rats as compared to the control group, and ASAA group showed the same as the normal group. 4. Both ASAA and NSAA groups did not show any changes of the creatinine clearance in multiple low-does STZ-induced diabetic rats. 5. Both ASAA and NSAA groups prevented the excretion of urinary glucose and albumin in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group showed more significant prevention than NSAA group. 6. Both ASAA and NSAA groups prevented the expansion of glomerular cells and the protein expression of transforming growth factor-${\beta}1$ in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group prevented more significantly than NSAA group.

• 한방안이비인후피부과학회지
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• 제23권1호
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• pp.94-110
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• 2010

Objective : This study was performed to evaluate the effect of immune reaction inductive substances such as phorbol-myristate-acetate(PMA), lipopolysaccharide(LPS), dermato-phagoides pteronyssus crude extract(DPE), dinitrochloro-benzene(DNCB) and Cryptotympana pustulata(CP), the Cryptotympana pustulata extracting substance at simultaneously on the translocation of nuclear factor-kappa B(NF-${\kappa}B$) towards to the nucleus and the mRNA expression patterns of various cytokine genes in Human acute monocytic leukemia cell line(THP-1 cells), monocytes of human. Experiment : To analyze cytokine genes expression patterns, the RT-PCR method was used, measuring tumor necrosis factor(TNF)-$\alpha$ that had been secreted during cell culture in the ELISA method. The morphological change in the cell observed during THP-1 cell culture was observed using a scanning electron microscope (SEM) and the quantitative distribution in the cell NF-${\kappa}B$ was analyzed through immunocytochemistry and a confocal microscopy. Result : CP showed different influences onto the mRNA expression patterns of cytokine genes with PMA, LPS. DPE and DNCB according to the types of immune inductive substances in the THP-1 cells. The expressions of inter-leukin(IL)-10, interferon(INF)-$\gamma$, TNF-$\alpha$ and monocyte chemoattractantant protein(MCP)-1 induced by PMA were suppressed by CP while the expression of transforming growth factor(TGF)-$\beta$ was promoted. Regarding the secretion pattern of TNF-$\alpha$ according to PMA processing, its secretion amount was increased by CP concurrent processing, in case of processing CP onto PMA and LPS, We discovered that the secretion amount of TNF-$\alpha$ was increased. Upon processing PMA and LPS on the THP-1 cell strain at the same time or either additionally processing CP thereon, the movement increase towards the nucleus from the NF-${\kappa}B$ cell cytoplasm, a transcription factor was able to be observed. Conclusion : In this study, Cryptotympana pustulata extracting substance was confirmed that it had an influence on expression patterns of cytokine genes according to the actions of a variety kinds of immune reaction inductive substances processed on the monocyte THP-1 cell of humans. Therefore, additional studies as for the immune adjusting function of Cryptotympana pustulata are considered to be able to offer important materials for curing immune abnormal diseases such as atopy dermatitis afterward.

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.1114-1124
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• 1997

연구배경 : Endothelin(이하 ET로 약함)은 폐혈관 내피세포에서 생산되며 강한 혈관 수축작용이 있는 peptide이다. 일차성 폐동맥고혈압과 급성 폐동맥색전증 환자의 혈장내 ET이 증가하고 이들 질환에서의 심폐기능장애에 ET이 중요한 역할을 하리라고 추측되나 ET증가의 기전에 대해서는 알려진 바 없다. 이들 두 질환은 모두 혈전증이 중요한 병태생리 소견이므로 저자들은 혈소판과 활성화된 혈소판에서 유리된 매개체들이 폐혈관 내피세포에서 ET 생산을 증가시킬 것이라고 가정하고 이를 확인하기 위하여 연구를 시행하였다. 방 법 : 소 폐동맥내피세포 배양배지에 혈소판, thrombin(0.1~10u/ml), transforming growth factor-${\beta}1$(TGF-${\beta}1$, 1-1000pM), serotonin(1-100uM), 및 내독소(1ug/ml)를 첨가한 후 18시간 배양하여 배지내로 유리된 immunoreactive ET(이하 ir-ET로 약함)을 방사선면역측정법으로 정량분석 하였다. 결과 : 소 폐동맥내피세포 배양 상청액내 ir-ET은 배양 시간에 비례하여 증가하였으며 혈소판 $10^8/ml$을 첨가한 군에서는 배양 8시간 및 18시간 후에 대조배지군에 비해 유의하게 높았다(p<0.05). 혈소판 첨가군에서 배양 상청액내 ir-ET은 혈소판의 수가 증가함에 따라 증가하는 경향을 보였고 $10^8/ml$에서는 대조배지군에 비해 유의하게 높았다 (0<0.05). Ir-ET를 증가시키지 않는 혈소판 ($10^7/ml$)에 ir-ET을 유의하게 증가시키지 않는 농도의 thrombin (0.1u/ml) 또는 내독소(1ug/ml)를 각각 첨가한 군에서 배양 상청액내 ir-ET은 배지 대조군과 단독 첨가군 (thrombin 0.1u/ml, 내독소 1ug/ml)에 비해 각각 유의하게 높았다(p<0.05). 소 폐동맥내피세포 배양 상청액내 ir-ET은 thrombin(1-10ug/ml), TGF-${\beta}1$(100-1000pM) 첨가군에서 각각 대조배지군에 비해 유의하게 높았으며 (p<0.05), serotonin(1-100uM) 첨가군은 대조배지군파 유의한 차이가 없었다. 결 론 : 소 폐동맥 내피세포에서 ET 생산을 자극하며 그 기전은 혈소판과 활성화된 혈소판에서 유리되는 TGF-${\beta}1$ 등의 매개물에 의한 내피세포의 자극으로 생각되며 이외에 혈소판에 의한 내피세포의 ET 생산 반응 조절(priming) 가능성도 추측할 수 있다.

• 셀메드
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• 제3권2호
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• pp.15.1-15.5
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• 2013

Previous reports showed that Compound Astragalus and Salvia miltiorrhiza extract (CASE), which was mainly composed of astragalosides, astragalus polysaccharide and salvianolic acids, inhibited hepatic fibrosis by mediating transforming growth factor-${\beta}$ (TGF-${\beta}$)/Smad signaling. Our aim was to examine the effects of CASE on D-galactosamine (D-GalN) treated liver injury in mice and carbon tetrachloride ($CCl_4$)-induced liver fibrosis in rats. CASE was administered to mice with D-GalN-induced liver injury and to rats with $CCl_4$-induced liver fibrosis, respectively. Liver injury was routinely evaluated by relative liver weight, serum levels of ALT, AST, hyaluronic acid (HA), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, hydroxyproline (HYP) and histopathologic changes. Treatment of mice with CASE (60, 120, and 240 mg/kg, ig) significantly lowered ALT, relative liver weight, and MDA levels when compared with D-GalN treated mice. CASE (120, 240 mg/kg) significantly lowered ALT, AST, HA, HYP, and MDA levels against $CCl_4$ treated rats. Decreased SOD level was reversed with CASE treatment. Upon histopathological examination, CASE treatment had significantly inhibitory effect on the progression of hepatic fibrosis in rats. These results indicate that CASE might be effective in treatment and prevention of acute and chronic hepatic injury due to its antioxidant activity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권4호
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• pp.325-336
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• 2000

Bone morphogenetic protein-2/4 are members of Transforming Growth Factor-$\beta$(TGF-$\beta$) superfamily and they may induce formation of cartilage and bone in vivo. This study was performed to investigate the cellular target and period of action of BMP-2/4 and understanding of actions of BMP-2/4 at cellular level. The appearance of BMP-2/4 during healing of mandibular and periodontal defect in rat was evaluated immunohistochemically. 40 Sprague-Dawley strain white male rats, each weighing about 300gm were used. Bony defect was performed in the mandible and they were sacrificed at the day of 3rd, 10th, 20th, 30th after operation. The specimens were harvested and examined histologically and immunohistochemically by localization of anti-BMP-2/4. The results were as follows: 1. Woven bone was observed at 10th day and perfect healing of defect with compact bone and periodontal ligment space at 30th day. 2. Osteoprogenitor cells, osteoblastic cells and periosteum were positive reaction to immunohistochemical stain at 10th day. 3. Cells of bone marrow space and surface cells of osteocytes and cementoblasts were positive reaction to immunohistochemical stain at 20th day. 4. Newly formed osteocytes and cementocytes were positive reaction to immunohistochemical stain at 30th day. From the above findings, we could conclude that BMP-2/4 acted significant roles as factors of induction, proliferation and differentiation during bone healing process.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권3호
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• pp.247-255
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• 2007

The bone morphogenic protein(BMP) can promote migration and growth of mesenchymal cells and initiate process for bone and cartilage formation. Cartilage-derived morphogenic protein(CDMP)-1 and -2 belong to the bone morphogenetic protein family in the transforming growth factor(TGF)-${\beta}$ superfamily. Although pleomorphic adenoma of the salivary glands is an epithelial tumor, it frequently shows ectopic cartilaginous formation with biomolecular studies. The mechanism of pathogenesis in cartilaginous formation is still controversy. We examined the expression and localization of CDMP-1 and -2, in comparison with the localization of cartilaginous matrix proteins, in human normal salivary glands and 20 cases of pleomorphic adenoma using immunohistochemical methods. The results were followed. 1. CMP-1 was immunolocalized in the striated ducts and the intercalated ducts, but not expressed in excretory duct, CDMP-2 was not expressed in the normal salivary glands. 2. CMP-1 was immunolocalized in the ductal cell and cuboidal neoplastic myoepithelial cells around the chondroid areas of the pleomorphic adenomas, whereas these molecules were not localized in the spindle-shaped neoplastic myoepithelial cells of the myxoid element in these tumors. CDMP-2 was expressed neither in normal salivary glands nor in any elements of the pleomorphic adenomas. 3. In transmission electron microscopic view, the tumor cells are composed of modifed myoepithelial cells between hyaline and myxoid stroma. 4. In Immuno-blot analysis, strong overexpression of CDMP-1 was frequently seen in pleomorphic adenomas, but the level of CDMP-2 was expressed minimally in pleomorphic adenoma. From the these results, it should be suggested that undifferentiated neoplastic myoepithelial cells around the chondroid areas expressed CDMP-1 and suggested that this molecule may play a role in the differentiation of neoplastic myoepithelial cells in pleomorphic adenoma, but not CDMP-2.