• Title/Summary/Keyword: TIMP2

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Effect of Greater Celandine (Chelidonium majus L.) on Rat Hepatic Stellate Cells with Liver Fibrosis (백굴채(白屈菜)가 간섬유화 과정 중 간성상세포에 미치는 영향)

  • Lee, Hong-Il;Kim, Young-Chul
    • The Journal of Internal Korean Medicine
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    • v.32 no.4
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    • pp.504-518
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    • 2011
  • Objectives : This study was performed to investigate the anti-fibrogenic effect of greater celandine on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells (HSC-T6) were treated with various concentrations of greater celandine extract for 24, 48, and 72 hours. The extraction was done with distilled water. After the treatment, cell viability, proliferation, mRNA of the ${\alpha}SMA$, TIMP-1, TIMP-2, collagen I ${\alpha}$ 1, MMP-2, IL-6, TGF-${\beta}1$, PDGFr-${\beta}1$, Bcl-2, Bax, Bcl-xl, caspase-3, caspase-9 and the activities of SOD and catalase were measured by using MTT assay, BrdU assay, real-time PCR, superoxide dismutase assay and catalase assay. Results : The viability, proliferation, mRNA expression and synthesis of collagen of the hepatic stellate cells were inhibited as the concentration increased, which indicates the herb has an inhibitory effect on fibrogenesis of the liver by regulating the fibrosis associated genes in transcription. Conclusions : These results suggest that greater celandine would be beneficial in the treatment of fibrotic patients as well as for patients with chronic hepatitis.

Analysis of Gene Expression in 4,4'-Methylenedianiline-induced Acute Hepatotoxicity

  • Oh, Jung-Hwa;Yoon, Hea-Jin;Lim, Jung-Sun;Park, Han-Jin;Cho, Jae-Woo;Kwon, Myung-Sang;Yoon, Seok-Joo
    • Toxicological Research
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    • v.25 no.2
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    • pp.85-92
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    • 2009
  • 4,4'-Methylenedianiline (MDA) is an aromatic amine that is widely used in the industrial synthetic process. Genotoxic MDA forms DNA adducts in the liver and is known to induce liver damage in human and rats. To elucidate the molecular mechanisms associated with MDA-induced hepatotoxicity, we have identified genes differentially expressed by microarray approach. BALB/c male mice were treated once daily with MDA (20 mg/kg) up to 7 days via intraperitoneal injection (i.p.) and hepatic damages were revealed by histopathological observation and elevation of serum marker enzymes such as AST, ALT, ALP, cholesterol, DBIL, and TBIL. Microarray analysis showed that 952 genes were differentially expressed in the liver of MDA-treated mice and their biological functions and canonical pathways were further analyzed using Ingenuity Pathways Analysis (IPA). Toxicological functional analysis showed that genes related to hepatotoxicity such hyperplasia/hyperproliferation (Timp1), necrosis/cell death (Cd14, Mt1f, Timp1, and Pmaip1), hemorrhaging (Mt1f), cholestasis (Akr1c3, Hpx, and Slc10a2), and inflammation (Cd14 and Hpx) were differentially expressed in MDA-treated group. This gene expression profiling should be useful for elucidating the genetic events associated with aromatic amine-induced hepatotoxicity and for discovering the potential biomarkers for hepatotoxicity.

Anti-Photoaging Effects of Angelica acutiloba Root Ethanol Extract in Human Dermal Fibroblasts

  • Park, Min Ah;Sim, Mi Ja;Kim, Young Chul
    • Toxicological Research
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    • v.33 no.2
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    • pp.125-134
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    • 2017
  • The effects that ultraviolet rays elicit on collagen synthesis and degradation are the most common causes of wrinkle formation and photo-aging in skin. The objectives of this study were to evaluate the effects of Angelica acutiloba root ethanol extract (AAEE) to promote collagen synthesis and inhibit collagen degradation in human dermal fibroblasts. By examining total polyphenol and flavonoid contents, electron donating ability, radical scavenging activity, and superoxide dismutase-like activity, we found that AAEE exhibited fairly good antioxidant activity. Treatment with AAEE significantly increased type I procollagen production by cultured fibroblasts, as well as reduced ultraviolet-induced matrix metalloproteinase-1 (MMP-1) expression and MMP-2 activity in a dose-dependent manner (p < 0.05). In addition, AAEE significantly increased TIMP-1 mRNA expression (p < 0.05), although without an associated dose-dependent increase in TIMP-1 protein expression. In summary, we suggest that AAEE may be a potentially effective agent for the prevention or alleviation of skin-wrinkle formation induced by ultraviolet rays.

The effect of medicinal herb administration to arthritis induced rabbit arthritistreatment (생약복합제제가 토끼의 퇴행성관절염 개선에 미치는 영향)

  • Kwon, Tae Dong;Kim, Ki Hoon
    • Journal of Nutrition and Health
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    • v.45 no.5
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    • pp.437-442
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    • 2012
  • The purpose of this study was is to investigate the arthritis treatment and prevention of the effects the herbral administration to experimental animals induces arthritis 4 weeks for medicinal herbs (Scutellaria baicalensis Georgi, Acanthopanacis cortex, Achyranthis Radix). To investigate the prevention of histopathological examination and molecular biological examinations for arthritis improvement in vivo New Zealand, white rabbits were divided into a normal (Normal, n = 7), or a collagen-induced arthritis (CIA, n = 7), or a collagenase injection and medicinal herbs (SAA, n = 7). It was confirmed that induced arthritis was treated with Gross examination, and the measurement of average arthritis index (MAI) and improved arthritis by medicinal herbs. TNF-${\alpha}$ and IL-$1{\beta}$ were significantly increased in the CIA and SAA groups, compared to the normal group (p < 0.05). MMP-1 and TIMP-2 were significantly increased in the CIA, compared to the other groups (p < 0.05). MMP-1 and TIMP-2 were significantly decreased in the SAA group, compared to the CIA group (p < 0.05). As a result, Herbal administration used in this study might be able to help in the treatment of arthritis induced by inflammatory and immunosuppressive effects, that which can be expected.

Matrix Metalloproteinase in Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증환자의 기관지폐포세척액 및 폐포대식세포 배양액의 Matrix metalloproteinase의 변화)

  • Park, Joo-Hun;Shim, Tae-Sun;Lim, Chae-Man;Koh, Youn-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.4
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    • pp.303-314
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    • 2001
  • Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

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Effect of Yinjinchunggan-tang(YJCGT) on Fibrogenesis in Thioacetamide(TAA)-induced Rat Liver Tissue (TAA로 유발된 간섬유화 동물모델에서 인진청간탕의 효과)

  • Park, Shin-Myoung;Lee, Jang-Hoon;Kim, Young-Chul;Woo, Hong-Jung
    • The Journal of Internal Korean Medicine
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    • v.30 no.2
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    • pp.270-287
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    • 2009
  • Objective : Yinjinchunggan-tang(YJCGT) is reported previously as having theraputic effects on hepatitis such as anti-implammatory, anti-apoptotic, anti-viral(HBV), etc. Though this prescription is not studied on its anti-fibrogenic effect, it is still expected to have the effect in the liver. Thus, this study was performed to investigate the anti-fibrogenic effect of YJCGT on thioacetamide(TAA)-induced liver fibrosis in rats. Method: Rat liver fibrosis was induced by intraperitoneal TAA injection(150mg/kg) 3 times a week for 5 weeks. After the YJCGT (YJCGT 1g/kg, YJCGT 2g/kg)-treatment, body weight, liver and spleen weights, liver function test, the complete blood count and the portal pressure were studied. In addition, gene expressions of ASMA, procollagen type Ia2, MMP2, TIMP1 and TIMP2, all of which are known to be associated with liver fibrosis, were analyzed by RT-PCR. After YJCGT (YJCGT 1g/kg, YJCGT 2g/kg) treatment, percentages of collagen in TAA-induced rat liver tissue were measured by image analyzer. Results : The body weight of the normal group increased more than that of the control and YJCGT-treated groups. The AST level of the YJCGT lg/kg-treated group significantly decreased compared to that of the control. The ALT and the GGT levels of the YJCGT 2g/kg-treated group significantly increased compared to those of the control. In the YJCGT-treated groups. WBC, RBC and Hgb elevated by TAA injection decreased but platelet count increased. In the YJCGT lg/kg-treated group, the portal pressure elevated by TAA injection significantly decreased. The significant decreases in the gene expressions of procollagen type Ia2, MMP2 and TIMP2 were observed in the YJCGT-treated groups. In histological findings. TAA injections caused severe liver fibrosis, but the YJCGT treatment significantly reduced the amounts of hepatic collagens. Conclusions: These results suggest that YJCGT has beneficial effects on the treatment of patients with liver cirrhosis as well as chronic hepatitis. Further study should be done to decide the optimal concentration of the YJCGT for the treatment of liver cirrhosis.

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