• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.107-116
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• 2002

Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.

• Journal of Applied Biological Chemistry
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• v.61 no.1
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• pp.9-15
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• 2018

We analyzed the antioxidant and anti-wrinkle activities of berberine, isolated from dried rhizome of Coptis japonica Makino, to determine its cosmetic potential. We performed the 3-[4,5-dimethylthiazol]-2-yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay to evaluate the toxicity of the berberine. We also measured the ROS and hyaluronic acid production, and expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and tumor necrosis factor-alpha ($TNF-{\alpha}$) to evaluate the antioxidant and anti-wrinkle activities of berberine, respectively. The cytotoxicity of ultraviolet light, in presence of berberine, was measured by the MTT assay using CCD-986sk fibroblasts, and no cytotoxicity was observed at concentrations less than $25{\mu}g/mL$. We also found that berberine decreased ROS production in a concentration-dependent manner and promoted the synthesis of hyaluronic acid. Further, berberine reduced the protein levels and mRNA expression of MMP-2 and MMP-9, which are associated with wrinkle formation, and increased the expression of TIMP-1 and TIMP-2. In addition, the inhibitory effect of berberine on $TNF-{\alpha}$, known as pro-inflammatory cytokine, was inhibited by $TNF-{\alpha}$ gene in a concentration-dependent manner. These results suggest that berberine holds cosmetic value owing to its antioxidant activity, by inhibiting ROS production and anti-wrinkle activity by reducing MMP-2 and MMP-9 and increasing TIMP-1 and TIMP-2 expression.

• Fisheries and Aquatic Sciences
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• v.15 no.2
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• pp.137-143
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• 2012

The abalone Haliotis discus hannai, is one of the economically important species in the fisheries industry. Abalone intestines are one of the by-products of its processing. To investigate its bioactive potential, abalone intestine was digested using an in vitro gastrointestinal (GI) digestion system containing pepsin, trypsin, and ${\alpha}$-chymotrypsin. The abalone intestine G1 digests (AIGIDs) produced by the GI digestion system were fractionated into AIGID I (> 100 kDa), AIGID II (10-100 kDa), and AIGID III (1-10 kDa) using an ultrafiltration membrane system. Of the three digests, AIGID II and AIGID III exhibited inhibitory effects against matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) in HT1080 human fibrosarcoma cells. Both fractions potently inhibited gelatine digestion by MMP-2 and MMP-9 treated with phorbol 12-myristate 13-acetate (PMA) and migration of HT1080 cells in dose dependently. Furthermore, AIGID II and III attenuated expression of p65, a component of nuclear transcription factor kappa B. These results indicate that of the abalone intestine digests inhibit MMP-2 and MMP-9. Thus, the AIGIDs or their active components may have preventive and therapeutic potential for diseases associated with MMP-2 and MMP-9 activation in fibrosarcoma cells.

• Journal of Ginseng Research
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• v.22 no.3
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• pp.216-221
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• 1998

We examined the anti-invasive activity of ginsenosides Rhl, Rha on the highly metastatic HT1080 human fibrosarcoma cell line. In vitro invasion assay showed ginsenoside Rhr reduced tumor cell invasion through a reconstituted basement membrane in a transwell chamber more than ginsenoside Rh1. Significant down-regulation of matrix metalloproteinase-9 (MMP-9) by ginsenosides Rh, and Rh2 was detected by Northern blot analysis. However, the expression of MMP-2 was not affected by Rh, and Rhr. The expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by Rhl after 0.5, 1 or 3 day-treatment but reduced after 6 day-treatment. However, the expression of TIMP-2 was not changed by treatment with Rh2. Plasminogen activator inhibitor (PAI) and urokinase-type plasmlnogen activator (uPA) were not changed by treatment with Rh1 and Rh2 for 3 and 6 days. Quantitative gelatin-based zymography confirmed a markedly reduced expression of MMP-9 but MMP-2 after treatments with ginsenosides Rhl and Rha. These results suggest that down-regulation of MMP-9 contributes to the anti-invasive activity of ginsenosides Rhl and Rhr in the HT1080 cells.

• Fisheries and Aquatic Sciences
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• v.21 no.6
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• pp.16.1-16.7
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• 2018

Background: Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content. Methods: In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells. S. horneri crude extract was fractionated with organic solvents, namely, water ($H_2O$), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solvent-partitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting. Results: All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography. Except $H_2O$ fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Conclusion: Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules.

• Tuberculosis and Respiratory Diseases
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• v.63 no.1
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• pp.31-41
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• 2007

Background: In pathogenesis and prognosis of lung cancer, significance of enormous types of genetic expression were very compounding and undetermined. We performed this study to search association between clinical characteristics and expression of COX-2, MMP-9 and p53 in non-small cell lung cancer. Methods: Ninety-one patients with adenocarcinoma or squamous cell carcinoma were enrolled. We had searched clinical data retrospectively and performed immunohistochemical staining for COX-2, MMP-9 and p53. We had analyzed significance of these three genes in clinical features and prognosis for survival. Results: 1) In squamous cell carcinoma, male was predominant and was significantly correlated with smoking. 2) Major prognostic determinants for overall survival were curative resection. 3) Expression of COX-2 was more frequent in adenocarcinoma than in squamous cell carcinoma. 4) Negative staining of COX-2, MMP-9 and p53 was more frequent in squamous cell carcinoma than adenocarcinoma. 5) Survival duration was longer in the group with positive expression of p53 and negative for COX-2 and MMP-9 (median duration of survival = 165.6 weeks) than groups with the other expressional patterns. 6) Significant correlation was found between expression of MMP-9 and COX-2. In squamous cell carcinoma, expression of MMP-9, COX-2 and mutant p53 were mutually correlated. 7) COX-2 expression was significant prognostic factor for survival in resected cancer group. In unresected inoperable non-small cell lung cancer group, MMP-9 was statistically significant prognostic factor for overall survival. Conclusion: COX-2 and MMP-9 might have some roles for progression or prognosis in some selected patients with non-small cell lung cancer. COX-2 and MMP-9 may have some roles for disease progression or prognosis in selected patients with NSCLC.

• Journal of Applied Biological Chemistry
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• v.63 no.1
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• pp.75-82
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• 2020

In this study, extracts from the Green ball apple peel (GBE) and the newly bred green ball apple from Korea showed inhibition effects on photo-aging factor regulation associated with skin aging. To investigate the inhibition effect on photo-aging factor regulation in skin, GBE was treated with UVB to induce photo-aging related factors in CCD986sk fibroblast cells. Photo-aging factor regulation effects showed that GBE inhibited UVB-stimulated matrix metalloproteinase (MMP)-1 and MMP-9 protein synthesis in collagen type I alpha 2 chain (COL1A2), MMP-1, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1 protein expression. The expression of COL1A2 and TIMP-1 protein was significantly increased. The mRNA expression levels of COL1A2, MMP-1, MMP-9, hyaluronan synthase (HAS)2, transforming growth factor (TGF)-β, and TIMP-1 were decreased by GBE. The expression of TIMP-1 and TGF-β, which are regulators involved in matrix metalloproteinase and type I procollagen expression, was found to increase with increasing expression of COL1A2. The expression of HAS2, which is involved in the production of hyaluronic acid, one of the structural proteins constituting the skin, was also confirmed. Therefore, GBE showed excellent efficacy against photo-aging factor regulation and could be used as functional material to prevent and treat skin aging.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.619-634
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• 2002

Background : Many inflammatory mediators and collagenases are involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The increase of matrix metalloproteinase-9 (MMP-9, gelatinase-B) produced mainly by inflammatory cells was reported in many ALI models and connective tissue cells. In this study, the expression of MMP-9 in ventilator-induced lung injury (VILI) model and the effects of matrix metalloproteinase inhibitor (MMPI) on VILI were investigated. Methods : Eighteen Sprague-Dawley rats were divided into three groups: low tidal Volume (LVT, 7mL/Kg tidal volume, 3 $cmH_2O$ PEEP, 40/min), high tidal volume (HVT, 30mL/Kg tidal volume, no PEEP, 40/min) and high tidal volume with MMPI (HVT+MMPI) groups. Mechanical ventilation was performed in room air for 2 hours. The 20 mg/Kg of CMT-3 (chemically modified tetracycline-3, 6-demethyl 6-deoxy 4-dedimethylamino tetracycline) was gavaged as MMPI from three days before mechanical ventilation. The degree of lung injury was measured with wet-to-dry weight ratio and acute lung injury score. Expression of MMP-9 was studied by immunohistochemical stain with a mouse monoclonal anti-rat MMP-9 $IgG_1$. Results : In the LVT, HVT and HVT+MMPI groups, the wet-to-dry weight ratio was $4.70{\pm}0.14$, $6.82{\pm}1.28$ and $4.92{\pm}0.98$, respectively. In the HVT group, the ratio was significantly higher than other groups (p<0.05). Acute lung injury score measured by five-point scale was $3.25{\pm}1.17$, $12.83{\pm}1.17$ and $4.67{\pm}0.52$, respectively. The HVT group was significantly damaged by VILI and MMPI protects injuries by mechanical ventilation (p<0.05). Expression of MMP-9 measured by four-point scale was $3.33{\pm}2.07$, $12.17{\pm}2.79$ and $3.60{\pm}1.95$, respectively, which were significantly higher in the HVT group (p<0.05). Conclusion : VILI increases significantly the expression of MMP-9 and MMPI prevents lung injury induced by mechanical ventilation through the inhibition of MMP-9.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4107-4113
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• 2013

Objective: Matrix metalloproteinase-9(MMP-9) plays an important role in tumor cell invasion. Although it has been studied frequently in ovarian cancer, its prognostic impact is still equivocal. The aim of this study was to more precisely estimate its prognostic significance. Method:We searched Pubmed, Embase, OVID, Sciencedirect and CBM databases to identify eligible studies. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were pooled across studies using fixed-effects or random-effects models. We also performed subgroup analysis. Results: 30 studies (n=2552 patients) focusing on prognosis or expression of MM-9 were included. Increased expression of MMP-9 was associated with poor prognosis in ovarian cancer patients (HR=1.68, 95%CI 1.09-2.59, p=0.02). Besides, MMP-9 expression in ovarian cancer was significantly higher than non-malignant tumors (OR=11.46, 95%CI 8.47-15.50, P<0.00001). Moreover, increased expression of MMP-9 was significantly associated with FIGO stage (OR=4.85, 95%CI 2.60-9.04, P<0.00001), grade of differentiation (OR=3.34, 95%CI 2.46-4.54, P<0.00001), lymph node metastasis (OR=5.75, 95%CI 3.71-8.92, P<0.00001) and there was no association with histological type of ovarian cancer. Conclusions: Increased expression of MMP-9 was associated with poor prognosis in ovarian cancer patients. Down-regulation of MMP-9 is an attractive therapeutic approach which might improve outcome of ovarian cancer.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.144-149
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• 2009

Chondrocytes and synovial fluid derived markers are used to monitor for osteoarthritis(OA). Specific inhibitors, known as tissue inhibitors of metalloproteinases(TIMP), regulate the proteolytic activity of matrix metalloproteinases(MMP). This study investigated whether MMP and TIMP levels were altered in synovial fluid and cartilage following the experimental induction of OA in canines. Twenty mature beagle dogs underwent a unilateral surgical transection of the cranial cruciate ligament and the medial collateral ligament as well as a medial meniscectomy. Matrix metalloproteinase-2 and MMP-9 levels were assayed using Western blot and TIMP-2 levels were measured with enzyme-linked immunosorbent assays four weeks after OA induction. Increased MMP-2 expression was observed in chondrocytes isolated from cartilage following OA induction, but MMP-9 expression decreased. Matrix metalloproteinase-2 and MMP-9 levels in synovial fluid from the OA induced joint significantly increased compared to those of the sham group. Tissue inhibitors of metalloproteinase-2 concentrations were higher in chondrocytes from the OA cartilage, yet TIMP-2 remained lower in the synovial fluid of OA. This suggests the elevated release of MMP-9 over MMP-2 into the synovial fluid following the cartilage degradation-related death of chondrocytes after OA. Osteoarthritis can be further deteriorated by increased MMP activity in the synovial fluid because TIMP-2 exist low concentration into the extracellular matrix. As a result, MMP activity, particularly MMP-9 activity, can be useful as a biomarker in diagnosing and monitoring the early stages of canine OA.