• 한국수의병리학회지
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• 제3권1호
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• pp.15-25
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• 1999

To elucidate the mechanism of age-related development in FGS/NgaKIST mice with spontaneous glomerulosclerotic lesion, we examined expression and localization of various cytokine mRNA in the kidney in the progression of diseases. This mouse model is the first to develop spontanously occuring glomerosclerotic lesion in the kidney. In this study, we detected the up-regulation of local cytokine genes such as IL-1$\beta$, IL-2, IL-6, IL-10, TNF-$\alpha$, TGF-$\beta$, and IFN- $\gamma$ in the kidneys. In RT-PCR and Southern blot analysis, we detected gradual expressions of cytokine mRNA of IL-1$\beta$, IL-2, IL-6, IFN- $\gamma$, and TNF $\alpha$ mRNA during the course of disease. Other cytokines including IL -10 and TGF -$\beta$ were found to be appeared the slightly expressed level at 3 to 12 weeks before onset of inflammatory lesion but they are highly expressed at the end-stage of the disease accompaning high proteinurea and wasting. In situ RT-PCR, each cytokine mRNA were specifically localized in a variety of cells including mesangial, endothelial, parietal epithelial, tubular epithelial, arterial muscle cell, and infiltrated inflammatory cells. In addition, TNF - $\alpha$was detected moderately in the visceral and parietal epithelial cell, but weakly in endothelial and mesangial cells, whereas IL-1 $\beta$ and IL -6 were strong in mesangial regions. IL-6 and TNF- $\alpha$ was highly localized in the damaged proximal and collecting tubules. Especially, TGF -$\beta$ mRNA was highly found in mesangial cells within glomerulus and interstitium during the end-stage of this disease.. These results indicate that pro inflammatory cytokines such as IL-1 $\beta$, IL-2, IL-6, and TNF- $\alpha$ were gradually expressed from the early stage of this disease to the end-stage, and that IL-10 and TGF-$\beta$ may be important in the accumulation of extracellular matrix(ECM) within glomerulus and periglomerular fibrosis in the progression of this disease as well as tissue destruction in end-stage of this disease.

• 생명과학회지
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• 제22권10호
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• pp.1371-1377
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• 2012

신장섬유화는 내 외부적인 요인들에 의해 발생하며, 그 요인들에 의해 염증이 생기고 지속적인 손상이 일어날 경우 신기능의 상실이 유발된다. 또한 신장섬유화는 세포 외 기질의 과다축적, TGF-${\beta}$나, TNF-${\alpha}$, IL-1과 같은 사이 토카인에 의해 발생하며, TGF-${\beta}$는 신장 섬유화의 과정과 Type I collagen과 fibronectin, PAI-1을 포함한 섬유화 관련 인자들의 발현 유도에 중요한 역할을 한다. 본 연구에서는 TGF-${\beta}$를 처리한 신장섬유화 유도 모델에서 Moringa oleifera Lam 추출물에 대한 섬유화 관련 인자들의 영향을 확인하였다. 실험 결과 TGF-${\beta}$로 유도된 신장 섬유화 세포에서 모링가 추출물이 fibronectin, Type I collagen과 PAI-1의 단백질 및 mRNA 발현을 저해하였으며, 모링가 추출물 중 모링가 뿌리추출물이 가장 영향이 있는 것으로 확인 되었다. 모링가 뿌리추출물이 어떠한 기전을 통하여 섬유화 관련 인자들의 발현을 조절하는지 알아보기 위한 TGF-${\beta}$로 유도된 $T{\beta}RII$ 및 그 하위 기전의 인산화 정도를 확인한 실험에서 모링가 뿌리추출물이 TGF-${\beta}$로 유도된 $T{\beta}RII$과 그 하위기전의 Smad4, ERK의 인산화를 저해하였다. 그러나 TGF-${\beta}$에 의해 유도된 JNK와 p38, PI3K/AKT의 인산화에는 영향이 없었다. 따라서 모링가 뿌리추출물이 TGF-${\beta}$로 유도된 신장 섬유아세포에서 $T{\beta}RII$와 그 하위 기전인 Smad4, ERK를 통해서 Type I collagen 과 fibronectin, PAI-1의 발현을 조절하여 섬유화를 저해 한다는 것을 예상할 수 있다. 결론적으로 모링가 뿌리추출물이 섬유화 치료 및 완화에 좋은 물질이 될 수 있을 것으로 생각된다.

• 한국동물위생학회지
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• 제28권2호
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• pp.91-98
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• 2005

Green tea was known which regulated adipocyte differentiation metabolism. The mechanism on the lipid decreased contents of TAG in the plasma. In addition, green tea increased the expression leptin mRNA, PPAR $\delta$ mRNA and TGF $\beta$. The tea tested was korean powdered green tea. In this experiment, Sprague-Dawley (SD) rats were fed $3\%$ green tea(powdered) for 3 weeks on the basal diet and obese diet and green tea grouts-fed pork meats. duck meats. The expression of leptin mRNA and PPAR $\delta$ mRNA were up-regulated in the green tea-fed groups compared with those of the not green tea-fed groups. There were no significantly difference on the expression of leptin mRNA and PPAR $\delta$ mRNA in green tea grouts-fed pork meats, duck meats as compared with the not fed green tea grouts meats. TGF $\beta$ mRNA. TNF $\alpha$ mRNA and adipsin mRNA were not expressed in the pork meats, duck meats. The expression of TGF $\beta$ mRNA, TNF $\alpha$ mRNA and adipsin mRNA were observed in the experimental rats but no significantly difference on the contents. Physiologic regulated genes were not expressed In the green tea grout-fed pork meats and duck meats.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2003년도 추계학술대회초록집
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• pp.16-16
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• 2003

Hepatic fibrosis is a common response to various chronic hepatic injuries and occurs as a consequence of the transformation of hepatic stellate cells into myofibroblasts (MFBs) producing abnormal extracellular matrix which is mainly induced by transforming growth factor-beta (TGF-${\beta}$), especially TGF-${\beta}$1 [1,2]. As the liver becomes fibrotic, there are both quantitative and qualitative changes in several pathological markers related to the hepatic fibrosis. These fibrotic markers in liver are mainly consisted of several proteins and cytokines, but sometimes included specific type cells. The aim of this study was to detect expression and change of markers (TGF-${\beta}$, mallory body, cytokeratin, ${\alpha}$-SMA, hypoxia, collagen) during hepatic fibrogenesis. (omitted)

• Clinical and Experimental Pediatrics
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• 제56권4호
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

• Tuberculosis and Respiratory Diseases
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• 제67권6호
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• pp.528-535
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• 2009

Background: Dust clouds blown by the wind from the arid deserts of Mongolia and Northeast China are known as Asian dust storms. Ambient particulate matter with a diameter <10 ${\mu}m$ ($PM_{10}$) is associated with the exacerbation of respiratory diseases and increased mortality of heart and lung disease patients. The fibrotic effects of $PM_{10}$ of Asian dust to pulmonary fibroblast cells are unknown. This study examined the production of reactive oxygen species (ROS), TGF-${\beta}$, NF-${\kappa}B$, PDGF-$\alpha$ and Fibronectin in fibroblasts exposed to Asian dust particles. Methods: Air samples were collected using a high volume air sampler (Sibata model HV500F) with an air flow of 500 L/min for at least 6 hours. The MRC-5 cells were exposed to 0, 50 and 100 ${\mu}g/mL$ of $PM_{10}$ for 24 hours. ROS was detected by measuring the level of oxidized DCF using FACS. TGF-$\beta$, NF-${\kappa}B$, PDGF-$\alpha$ and fibronectin were detected by western blotting. Results: There was no increase in the ROS, TGF-$\beta$ and PDGF-$\alpha$ levels in the MRC-5 cells exposed to $PM_{10}$. The NF-${\kappa}B$ level was higher in the MRC-5 cells exposed to 50 and 100 ${\mu}g/mL$ of $PM_{10}$ for 24 hours. The fibronectin level in the MRC-5 cells after 24 hours incubation with 50 ${\mu}g/mL$ $PM_{10}$ was significantly higher than the control group ($PM_{10}$ 50 ${\mu}g/mL$ 113.27${\pm}$8.65 of control, p=0.005). Conclusion: $PM_{10}$ from Asian dust increases the activation of NF-${\kappa}B$ and fibronectin expression in MRC-5 fibroblast cells.

• Journal of Chest Surgery
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• 제44권6호
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• pp.406-412
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• 2011

Background: Development of thoracic aortic aneurysms and aortic dissections (TAAD) is attributed to unbearable wall tension superimposed on defective aortic wall integrity and impaired aortic repair mechanisms. Central to this repair mechanisms are well-balanced and adequately functional cellular components of the aortic wall, including endothelial cells, smooth muscle cells (SMCs), inflammatory cells, and adventitial fibroblasts. Adventitial fibroblasts naturally produce aortic extracellular matrix (ECM), and, when aortic wall is injured, they can be transformed into SMCs, which in turn are involved in aortic remodeling. We postulated the hypothesis that adventitial fibroblasts in patients with TAAD may have defects in ECM production and SMC transformation. Materials and Methods: Adventitial fibroblasts were procured from the adventitial layer of fresh aortic tissues of patients with TAAD (Group I) and of multi-organ donors (Group II), and 4-passage cell culture was performed prior to the experiment. To assess ECM production, cells were treated with TNF-${\alpha}$ (50 pM) and the expression of MMP-2/MMP-3 was analyzed using western blot technique. To assess SMC transformation capacity, cells were treated with TGF-${\beta}1$ and expression of SM ${\alpha}$-actin, SM-MHC, Ki-67 and SM calponin was evaluated using western blot technique. Fibroblasts were then treated with TGF-${\beta}1$ (10 pM) for up to 10 days with TGF-${\beta}1$ supplementation every 2 days, and the proportion of transformed SMC in the cell line was measured using immunofluorescence assay for fibroblast surface antigen every 2 days. Results: MMP-3 expression was significantly lower in group I than in group II. TGF-${\beta}1$-stimulated adventitial fibroblasts in group I expressed less SM ${\alpha}$-actin, SM-MHC, and Ki-67 than in group II. SM-calponin expression was not different between the two groups. Presence of fibroblast was observed on immunofluorescence assay after more than 6 days of TGF-${\beta}1$ treatment in group I, while most fibroblasts were transformed to SMC within 4 days in group II. Conclusion: ECM production and SMC transformation are compromised in adventitial fibroblasts from patients with TAAD. This result suggests that functional restoration of adventitial fibroblasts could well be a novel approach for the prevention and treatment of TAAD.

• 동의생리병리학회지
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• 제23권3호
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• pp.619-630
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• 2009

To investigate the hair growth activity of fractions and extract of Arisaematis Rhizoma in the hair removed skin of normal and spontaneous alopecia areata model in C57B/6N mice. These experiments were performed with the macroscopic, microscopic, immunohistochemical(VEGF, c-kit, PKC-${\alpha}$, TGF and FGF) and RT-PCR(TGF-${\beta}$, IGF, prolactin and placenta lactogen) methods. The results were as follows: Macroscopic observation after topical application of vehicle, 50% EtOH as control and extract of Arisaematis Rhizoma to the hair removed skin of C57BL/6N mice on the 9th, 11th and 15th day. Extensive hair growth activity was observed in treated group with extract of Arisaematis Rhizoma on the 9th, 11th and 15th day. In Arisaematis Rhizoma extracts treated group, hair follicles of middle stage of anagen was observed and it were grown down to subcutaneous tissue of skin in all the normal mice on 15th day. But in control group, most of hair follicles of telogen phase was observed in skin. The treatment of extract of Arisaematis Rhizoma increased expression of IGF(145%) and placenta lactogen(108%) in the skin of normal C57BL/6N mice on the 11th day compared to control group(100%). But expression of TGF-${\beta}$(90%) and prolactin(91%) decreased in the skin of normal C57B/6N mice on the 11th day compared to control group(100%). After application of fractions(chloroform, ethyl acetate and water fractions) of Arisaematis Rhizoma extract for 9th day, hair growth effect was observed in whole skin area in 50% of normal mice. But in control group, hair growth effect was not observed in whole skin area of normal mice. Immunoreactive density of VEGF, c-kit, PKC-${\alpha$ and FGF in skin of fractions of Arisaematis Rhizoma extracts was strongly stained in epidermis, bulge, secondary hair germ cells, cutaneous trunci m., subcutaneous tissue, root sheath compare to control group on the 9th day. In spontaneous alopecia areata model, The hair growth activity of Arisaematis Rhizoma extrat treated group(75%) was observed to be strong compared to control group(O%) on 7th day. These experiments suggest that fractions and extracts of Arisaematis Rhizoma may stimulate the topical hair growth activity. Thus it can be useful for treatment of alopecia areata.

• 동의신경정신과학회지
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• 제18권1호
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• pp.185-196
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• 2007

Objective : This experimental Study was designed to investigate the effects of FOENICULI FRUCTUS(FF) on the change of inhibition lactate dehydrogenase(LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. Method : FOENICULI FRUCTUS(FF)freeze dry powder and FF on the LDH activity in neuronal cells. Changes of FF on the physiological parameters(PaO2, PaCO2, MABP and HR) in crerbral ischemic rats. Effects of FF on the IL-1beta production, $TNF-{\alpha}$ production, $TGF-{\beta}$ production, and IL-10 in serum of cerebral ischemic rats. MCAO :. cytokines production of serum by drawing from femoral arterial blood after MCAO 1 hr. Reperfusion : cytokines production of serum by drawing from femoral arterial blood after reperfusion 1 hr. Results and Conclusion : 1. FF did not inhibit lactate dehydrogenase(LDH) activity in neuronal cells. 2. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) 1 hr and reperfusion 1 hr, sample group was significantly decreased $IL-l{\beta}$ production compared with control group 3. In serum by drawing from femoral arterial blood after MCAO 1 hr and reperfusion 1 hr, sample group was significantly decreased $TNF-{\alpha}$ production compared with control group. 4. In serum by drawing from femoral arterial blood after MCAO 1 hr and reperfusion 1 hr, sample group was significantly increased $TGF-{\beta}$ production compared with control group. 5. In serum by drawing from femoral arterial blood after reperfusion 1 hr, sample group was significantly increased IL-10 production compared with control group. This results were suggested that FF had inhibitive effect on the brain damage by inhibited LDH activity, $IL-l{\beta}$ and $TNF-{\alpha}$production, but accelerated $TGF-{\beta}$ production and IL-10 production.

• 대한의생명과학회지
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• 제19권3호
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• pp.195-205
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• 2013

Obesity may cause metabolic syndrome and adult diseases. This study was undertaken to investigate the ameliorative or useful effects of beanleaves on inflammation and liver damage in obese rat models. Rats were divided into three groups: a control group (normal diet, n=6), a fat diet group (45%-fat diet, n=7), and a bean leaf group (45%-fat+Korean bean leaves diet, n=7). Body weights in the bean leaf group were lower than those of the fat group (P<0.05). Serum tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and prostaglandin $E_2$ ($PGE_2$) concentrations were lower in both the control and bean leaf groups than in the fat group (P<0.001). TNF-${\alpha}$ concentrations in the bean leaf group were slightly higher than in the control group but statistically significant (P<0.05). The bean leaf group histologically exhibited lower fatty degeneration, spotty necrosis, and leukocyte infiltrations in hepatic tissues than those of the fat group. In the homogenized liver tissues, the cyclooxygenase-2 (COX-2) gene was only expressed in the fat group. The gene expression levels of hepatic TNF-${\alpha}$, inducible nitric-oxide synthase, peroxiome proliferator-activated receptor-${\alpha}$ (PPAR-${\alpha}$), poly (ADP-ribose) polymerase (PARP), and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) were weaker in the bean leaf group than in the fat group. These results suggest that adding bean-leaves to the diet may ameliorate obesity-induced systemic inflammation and liver damage and that bean leaves may be a useful food for preventing obesity and thereby metabolic syndrome and adult diseases.