• 생명과학회지
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• 제32권1호
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• pp.51-55
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• 2022

Matrix metalloproteinases (MMPs)는 세포의 기저막 분해에 관여하는 효소로 과발현된 MMPs는 암세포 침윤과 전이에 직접적인 영향을 주는 것으로 알려져 있다. 본 연구에서는 항산화, 항염증, 항균활성 있는 것으로 보고되어 있는 염주괴불주머니 추출물을 이용하여 PMA로 유도된 인간 섬유육종세포 HT-1080 세포에서 MMP-2, MMP-9의 발현 조절에 미치는 영향을 확인하였다. 그 결과 염주괴불주머니 추출물은 TIMP-1 및 TIMP-2를 증가시키면서 MMP-2 및 MMP-9의 mRNA 및 단백질 발현 수준을 모두 감소시키는 것으로 나타났다. 또한 p38, JNK, ERK의 인산화를 억제하였으며, 이를 통해 염주괴불주머니 추출물은 MAPKs 신호 전달 경로 조절에 영향을 줌으로써 MMPs 발현을 감소시키는 것을 확인할 수 있었다. 따라서 이러한 연구의 결과는 염주괴불주머니를 이용한 암 전이 억제 소재 개발을 위한 기초자료로 활용될 수 있을 것으로 기대된다.

• 한국발생생물학회지:발생과생식
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• 제5권2호
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• pp.123-129
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• 2001

포유동물의 난포내 난자의 성숙 시에는 난자를 둘러싸고 있는 난구세포의 확장 현상이 일어나는데 이 현상에는 hyaluronic acid 뿐만 아니라 다른 성분도 관여하는 것으로 알려져 있다. 본 연구는 조직 재구성 과정에서 중요한 역할을 하는 matrix metalloproteinase(MMP)가 사람의 성숙한 난자-난구 복합체의 extracellular matrix(ECM)에 존재하는지의 여부를 알아보고자 하였다. 체외수정 시술 시에 얻어지는 사람의 난자-난구 복합체를 재료로 zymography와 western blotting 방법으로 조사한 결과 난자-난구 복합체의 ECM에는 300kDa, 240kDa, 200kDa, 180kDa, 116kDa, 97kDa, 그리고 84kDa의 분자량을 갖는 적어도 7종류의 gelatinase들이 존재하는 것이 관찰되었다. 이들 gelatinase가 MMP인지를 확인하기 위해 zymography 동안에 ethylenediaminetetraacetic acid 혹은 phenanthroline 등의 MMP 억제제를 처리한 결과 7종류 모두의 gelatinase 효소활성이 사라졌다. 또한 MMP의 활성제인 aminophenylmercuric acetate를 zymography를 시행하기 전에 ECM에 처리한 결과 200kDa, 180kDa, 97kDa, 84kDa의 gelatinase활성이 사라지고, 대신에 80kDa, 65kDa, 60kDa의 분자량을 갖는 새로운 gelatinase 단백질의 효소활성이 나타났다. 이로 미루어 사람 난자-난구 복합체의 ECM에는 여러 종류의 gelatinase들이 있으며 이들 중 일부는 MMP-2와 MMP-9의 동위효소들인 것으로 여겨진다.

• 한국식품영양과학회지
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• 제42권8호
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• pp.1167-1174
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• 2013

암세포를 포함한 생체 내 빠른 분열을 요구하는 세포 집단에서 세포 내 구성요소 및 에너지원으로서 글루타민의 요구량이 증대되지만, 종양세포의 글루타민 의존적 대사작용에 관한 기전은 여전히 잘 알려진 바 없다. 본 연구에서는 LnCaP 전립선 암세포의 이동성 및 침윤성에 미치는 글루타민 결핍효능을 조사하였다. 본 연구의 결과에 의하면 LnCaP 세포에서 글루타민 결핍에 의하여 세포의 이동성 및 세포의 침윤성이 현저하게 억제되었으며, 이러한 이동성 및 침윤성 억제는 TIMPs의 발현 증대에 의한 MMPs의 발현 감소 및 그들의 효소적 활성 저하와 연관성이 있었다. 또한 글루타민이 결핍된 조건에서 배양된 LnCaP 세포에서 TER의 현저한 증가가 관찰되었는데, 이는 TJs의 조절인자인 claudin family 발현의 차단에 의한 것으로 생각되어진다. 본 연구의 결과에 의하면 암세포의 증식에서 글루타민의 결핍은 TJ의 결합력 증대와 MMPs의 활성을 저하시킴으로써 암세포 전이에 가장 기본적인 과정인 암세포의 이동성과 침윤성을 억제시킬 수 있을 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.391-396
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• 2014

Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

• 한국임상수의학회지
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• 제18권3호
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• pp.304-310
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• 2001

The joint disease including osteoarthris (OA) and rheumatoid arthritis (RA) are common in the horse. Many studies have been performed to develop biochemical markers reflecting the abnormalities of cartilage and synovial membrane. However, no specific, sensitive and clinically well established assay systems have been yet available to characterize the severity of joint diseases. Indeed, radiography is still doctor's best choice of assessing joint damage in OA/RA. This review focuses on biochemical molecules such as proteoglycan, collagen, matrix metalloproteinases (MMPs), lectin and cytokine to assess their potential value for not only predicting stage of joint disease but also monitoring treatment efficacy.

• Environmental Analysis Health and Toxicology
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• 제24권1호
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• pp.63-70
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• 2009

Naringenin, major one of the citrus flavonoids, have been identified that exert antioxidative, anticancer effects. The present study investigated the effects of naringenin on tumor invasion and matrix metalloproteinases(MMPs) activities. Naringenin inhibited cell invasion of HT-1080 fibrosarcoma cells in a dose-dependent manner. The activities of MMP-2 and MMP-9 were inhibited by naringenin as demonstrated by gelatin zymography assay. Furthermore, the amounts of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed in the cells. MMP-2, MMP-9, and MT1-MMP mRNA expression were suppressed by naringenin with time and dose-dependent. These results demonstrate that anti-metastatic activities of naringenin resulted from blocking of invasion of the HT-1080 cells. Taken together, the results of this studies provide evidence that naringenin possess an anti-metastatic activity.

• Nutrition Research and Practice
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• 제8권4호
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• pp.398-403
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• 2014

BACKGROUND/OBJECTIVES: Ultraviolet B (UVB) irradiation on skin can induce production of reactive oxygen species (ROS), which cause expression of matrix metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of skin to UVB irradiation leads to histological changes consistent with aging, such as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the protective effect of the standardized green tea seed extract (GSE) on UVB-induced skin photoaging in hairless mice. MATERIALS/METHODS: Skin photoaging was induced by UVB irradiation on the back of Skh-1 hairless mice three times per week and UVB irradiation was performed for 10 weeks. Mice were divided into six groups; normal control, UVB irradiated control group, positive control (UVB + dietary supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE 10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200 mg/kg (UVB + dietary supplement of GSE 200 mg/kg). RESULTS: The dietary supplement GSE attenuated UVB irradiation-induced wrinkle formation and the decrease in density of dermal collagen fiber. In addition, results of the antioxidant analysis showed that GSE induced a significant increase in antioxidant enzyme activity compared with the UVB irradiation control group. Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and type-1 collagen. CONCLUSIONS: Findings of this study suggest that dietary supplement GSE could be useful in attenuation of UVB irradiation-induced skin photoaging and wrinkle formation due to regulation of antioxidant defense systems and MMPs expression.

• 한국수정란이식학회지
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• 제33권2호
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• pp.61-68
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• 2018

The major focus of this study is to analyze the expression of bovine MMPs and to monitor their activity during the estrus cycle and pregnancy. During pregnancy, MMP-2 expression was detectable around 30 days but became insignificant by 60 days, then started to increase again around 90 days and reached the maximum at 250 days. The activity of MMP-2 protein changed in accordance with its expression level. As expected, the level of TIMP-2 exhibited a reverse pattern. About MMP-9, high level expression was observed as early as 30 days and gradually increase until 90 days. Then started to decrease after 250 days. Again, the sites of MMP-9 expression were similar to those of MMP-2. On the other hand, expression of TIMP-3 remained low until 90 days but showed a small and temporal increase around 250 days. In summary, expression of different MMPs were differentially regulated during estrus cycle and pregnancy. While the expression of MMP-2 was high in estrus cycle, MMP-9 slowly takes over with the progression of pregnancy. These results indicated that the luteal tissue perform distinct functions during pregnancy and estrus. Perhaps the activity of MMP-2 is required for the structural remodeling of luteum, resulting the suppression of P4 inflow from blood. On the other hand, steady maintenance of MMP-9 throughout luteal development is important for the activation of cell proliferation, maturation and angiogenesis.

• Molecules and Cells
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• 제22권1호
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• pp.104-112
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• 2006

We previously reported that DA-9601, ethanol herbal extract of Artemisia asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast cells activated with specific antigen/antibody reaction. This study aimed to evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation in allergic asthma mouse model. BALB/c mice were sensitized and challenged with OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA-specific serum IgE was measured by ELISA, recruitment of inflammatory cells in BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell hyperplasia by PAS staining, activities of MMPs by gelatin zymography, expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of MAP kinases by western blot, and activity of NF-${\kappa}B$ by EMSA. DA-9601 reduced IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues, expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs activity, expressions of mRNA and productions of various cytokines, activities of MAP kinases and NK-${\kappa}B$ increased from OVA-challenged mice. These data suggest that DA-9601 may be developed as a clinical therapeutic agent in allergic diseases due to suppressing the airway allergic inflammation via regulation of various cellular molecules expressed by MAP kinases/NF-${\kappa}B$ pathway.

• KSBB Journal
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• 제18권1호
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• pp.25-29
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• 2003

더덕의 메탄올 추출물(CL-ex)이 혈관신생에 영향을 주는 지의 여부를 알아보기 위하여, 인간태반 정맥내피세포와 돼지 폐동맥내피세포를 이용하여 실험하였다. 실험 결과, 더덕추출물은 FGF에 의해 유도된 시험관 내 혈관신생을 억제하였다. 또한 더덕추출물은 내피세포의 DNA 합성에는 영향을 주지 않았으나, FGF에 의해 증가된 내피세포의 이동을 농도 의존적으로 강하게 억제하였고, MMPs의 분비 역시 감소시켰다. 이러한 결과에 의하면, 더덕에 함유된 혈관신생 억제 물질은 혈관내피세포의 이동 과정에 작용하여 그 효과를 나타내는 것이라 추정된다. 따라서 더덕은 그 발생과 진행이 혈관신생에 의존하고 있는 것으로 알려진 암 등의 질병 예방과 치료를 위한 유용한 식물자원으로 개발될 수 있음을 시사한다.