• Journal of Acupuncture Research
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• v.22 no.2
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• pp.191-201
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• 2005

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.115-122
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• 2020

Background: In aged skin, degradation of collagen fibers, which occupy the majority of the extracellular matrix in the dermis, and changes of aquaporin 3 (AQP3) and skin constituents, such as hyaluronic acid and ceramide, cause wrinkles and decrease skin moisturization to contribute to dryness and lower elasticity skin. Red ginseng (RG) is used as a cosmetic and food material and is known to protect from UVB-induced cell death, increase skin hydration, prevent wrinkles, and have an antioxidative effect. But, in general, RG used as a material is the soluble liquid portion in the solvent, and the part that is not soluble in the solvent is discarded. Thus, we made the whole RG into microgranulation and dispersed in water to produce gel form for using entire RG, and it was named red ginseng NaturalGEL (RG NGEL). Methods: RG NGEL was investigated for matrix metalloproteinases inhibitory activity, induction of Type I collagen, AQP3, hyaluronan synthetase 2, serine palmitoyl transferase, ceramide synthase 3, and filaggrin expression and compared with RG water extract. Results: RG NGEL reduced the levels of UV-induced matrix metalloproteinases and increased Type I collagen in human fibroblast cells and upregulated AQP3, hyaluronan synthetase 2, serine palmitoyl transferase, ceramide synthase 3, and filaggrin expressions in human keratinocytes compared with RG water extract. Conclusion: RG NGEL has the potential as an effective reagent for antiaging cosmetics to improve wrinkle formation and skin hydration.

• Molecules and Cells
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• v.42 no.3
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• pp.218-227
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• 2019

This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient ($ApoE^{-/-}$) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.

• Korean Journal of Head & Neck Oncology
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• v.18 no.2
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• pp.135-141
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• 2002

Backgrounds and Objectives: Metastasis is a complex multistep process that requires sequential interactions between the invasive cell and the extra-cellular matrix. Transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) is a multifunctional regulator of cellular differentiation, motility and growth. Loss of sensitivity to the growth inhibitory effects by $TGF-{\beta}1$ plays important roles in neoplastic progression. The aim of this study was to investigate the role of $TGF-{\beta}1$ in the neoplastic invasion and metastasis through matrix metalloproteinase (MMP) of laryngeal cancer cell lines. Material and Methods: Two laryngeal cancer cell lines, SNU-899 and SNU-1076 were treated with recombinant $TGF-{\beta}1$, and the expression of MMP-2 and MMP-9 was immunohistochemically evaluated and gelatinase activity was studied by gelatin zymogram. Results: The cell growth inhibition was evident on 4th days after 1ng/ml and 10ng/ml $TGF-{\beta}1$ treatment. The expressions of MMP-2 and MMP-9, and their gelatinase activities were increased in dose-dependent manner. Conclusion: $TGF-{\beta}1$ treatment in laryngeal cancer cell lines induces the expression of MMP-2 and MMP-9, thus playing a role in the digestion of extracellular matrix gelatin.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.3
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• pp.334-342
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• 2013

Proteases and protease inhibitors play key roles in most physiological processes, including cell migration, cell signaling, and cell surface and tissue remodeling. Among these, the matrix metalloproteinase (MMPs) pathway is one of the most efficient biosynthetic pathways for controlling the activation of enzymes responsible for protein degradation. This also indicates the association of MMPs with the maturation of spermatozoa. In an attempt to investigate the effect of MMP activation and inhibitors in cultures with various hormones during sperm capacitation, we examined and monitored the localization and expression of MMPs (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-2 and TIMP-3), as well as their expression profiles. Matured spermatozoa were collected from cultures with follicle-stimulating hormone (FSH), luteinizing hormone (LH), and Lutalyse at 1 h, 6 h, 18 h, and 24 h. ELISA detected the expression of MMP-2, MMP-9, TIMP-2, and TIMP-3 in all culture media, regardless of medium type (FSH-supplemented fertilization Brackett-Oliphant medium (FFBO), LH-supplemented FBO (LFBO), or Lutalyse-supplemented FBO (LuFBO)). TIMP-2 and TIMP-3 expression patterns decreased in LFBO and LuFBO. MMP-2 and MMP-9 activity in FBO and FFBO progressively increased from 1 h to 24 h but was not detected in LFBO and LuFBO. The localization and expression of TIMP-2 and TIMP-3 in sperm heads was also measured by immunofluorescence analysis. However, MMPs were not detected in the sperm heads. MMP and TIMP expression patterns differed according to the effect of various hormones. These findings suggest that MMPs have a role in sperm viability during capacitation. In conjunction with hormones, MMPs play a role in maintaining capacitation and fertilization by controlling extracellular matrix inhibitors of sperm.

• Animal Bioscience
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• v.36 no.8
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• pp.1167-1179
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• 2023

Objective: Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Results: Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. Conclusion: These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.

• Childhood Kidney Diseases
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• v.15 no.2
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• pp.116-124
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• 2011

Acute kidney injury (AKI) can result in mortality or progress to chronic kidney disease in hospitalized patients. Although serum creatinine has long been used as the best biomarker for diagnosis of AKI, it has some clinical limitations, especially in children. New biomarkers are needed for early diagnosis, differential diagnosis, and reliable prediction of prognosis in AKI. Up to the present, candidate AKI biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), livertype fatty acid-binding protein (L-FABP), matrix metalloproteinase-9 (MMP-9), and Nacetyl-$\ss$-D-glucosaminidase (NAG). However, whether these are superior to serum creatinine in the confirmation of diagnosis and prediction of prognosis in AKI is unclear. Further studies are needed for clinical application of these new biomarkers in AKI.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• Journal of Life Science
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• v.15 no.2 s.69
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• pp.231-235
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• 2005

Matrix metalloproteinases (MMPs) are a family of structurally and functionally related zinc-dependent enzymes responsible for proteolytic degradation of extracellular matrix components such as base membrane or interstitial stroma. MMPs play an important role in a variety of physiological and pathological tissue remodeling processes, including wound healing, embryo implantation, tumor invasion and metastasis. Since MMP-9 (gelatinase B) has unique ability to cleave type IV collagen, gene expression of MMP-9 has been focused on as a pharmacological target. Flavonoids are a class of compounds that are widely spread in plants. In the coures of screening for the suppressors of MMP-9 gene expression from natural products, Metasequoia glyptostroboides was selected. Six flavonoids, sciadopitysin, isoginkgetin, bilobetin, 2,3-dihydrohinokiflavone, luteolin and apigenin were purified as suppressors of MMP-9 gene expression from M. glyptostroboides. The suppressing activity of the isolated flavinoids on the MMP-9 gene expression was measured by gelatin zymography and Nothern blot analysis.

• Journal of Pharmacopuncture
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• v.21 no.3
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• pp.177-184
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• 2018

Objectives: Auraptene, a natural citrus coumarin, found in plants of Rutaceae and Apiaceae families. In this study, we investigated the effects of auraptene on tumor migration, invasion and matrix metalloproteinase (MMP)-2 and -9 enzymes activity. Methods: The effects of auraptene on the viability of A2780 and Hela cell lines was evaluated by MTT assay. Wound healing migration assay and Boyden chamber assay were determined the effect of auraptene on migration and cell invasion, respectively. MMP-2 and MMP-9 activities were analyzed by gelatin zymography assay. Results: Auraptene reduced A2780 cell viability. The results showed that auraptene inhibited in vitro migration and invasion of both cells. Furthermore, cell invasion ability suppressed at $100{\mu}M$ auraptene in Hela cells and at 25, $50{\mu}M$ in A2780 cell line. Gelatin zymography showed that for Hela cell line, auraptene suppressed MMP-2 enzymatic activity in all concentrations and for MMP-9 at a concentration between 12.5 to $100{\mu}M$ in A2780 cell line. Conclusion: Auraptene inhibited migration and invasion of human cervical and ovarian cancer cells in vitro by possibly inhibitory effects on MMP-2 and MMP-9 activity.