• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6199-6203
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• 2014

Background: The expression of MMP genes has been demonstrated to be associated with tumor invasion, metastasis and survival rate for a variety of cancers. The functional promoter polymorphism MMP-2 C-735T is associated with decreased expression of the MMP-2 gene. The aim of present study was to detect any association between MMP-2 C-735T and susceptibility to breast cancer. Materials and Methods: The MMP-2 C-735T polymorphism was studied in 233 women (98 with breast cancer and 135 healthy controls). All studied women were from Kermanshah and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MMP-2 CC, CT and TT genotypes in healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed (p=0.077). In patients the frequency of the MMP-2 C allele was significantly higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI 1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in patients ${\leq}40$ years (88.9%) than those aged ${\geq}41$ years (67.5%, p=0.07). In addition, the frequency of MMP-2 C allele tended to be higher in patients with a family history of cancer in first-degree relatives (76.6%) compared to that without a family history of cancer (67.3%, p=0.31). Conclusions: Our findings indicate that the C allele of MMP-2 C-735T polymorphism is associated with increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk of young onset breast cancer in our population.

• 동의생리병리학회지
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• 제21권1호
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• pp.243-249
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• 2007

The French paradox has been attributed to the antioxidant properties of flavonoids present in the red wine. Amentoflavone(AF) is a bi-flavonoid compound with anti-fungal and anti-inflammatory activities. We isolated AF from Selaginella tamariscina, and studied its effects on nuclear factor-B(NF-B)-mediated MMP-9 gene expression in RAW264.7 cells. AF blocked the lipopolysaccharide(LPS)-induced expression of MMP-9. Zymographic and immunoblot analyses showed that AF suppressed LPS-induced MMP-9 expression in a dose-dependent manner. To clarify the mechanistic basis for its inhibition of MMP-9 induction, we examined the effect of AF on the transactivation of MMP-9 gene by luciferase reporter activity using -1.59 kb flanking region. AF potently suppressed the reporter gene activity. This inhibition was characterized by down-regulation of MMP-9, which was transcriptionally regulated at NF-B site and activation protein-1 (AP-1) site in the MMP-9 promoter, two important nuclear transcription factors that are involved in MMP-9 expression. These findings indicate the efficacy of AF in inhibiting MMP-9 expression through the transcription factors NF-B and AP-1 on LPS-induced RAW264.7 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.643-646
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• 2014

Objective: This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Methods: Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. Results: TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR-2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. Conclusion: TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

• 동의생리병리학회지
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• 제20권1호
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• pp.37-42
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• 2006

Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants such as lipopolysaccharide (LPS) leads to the production of significant amounts of MMP-9. Here, we show that LPS-induced MMP-9 production and activation was inhibited by the water extract from the fruit of Chaenomeles sinensis (CS), the root of Polygonum cuspidatum (PC), but increased by the extract from Boswellia carterii (BC). To investigate the mechanism by which those extracts inhibits MMP-9 activation, we examined the level of MMP-9 mRNA expression. We observed a significant change in the MMP-9 expression between LPS alone and LPS plus Chaenomeles sinensis and Polygonum cuspidatum extracts-treated cells. In addition, LPS significantly up-regulated MMP-9 promoter activity in Raw 264.7 cells, which was attenuated by the CS and PS extracts. However, water extracts from Boswellia carterii increased MMP-9 expression and MMP-9 promoter activity which were induced by LPS treatment in Raw 264.7 cells. These data suggest that water extracts from Chaenomeles sinensis and Polygonum cuspidatum can modulate anti-inflammatory immune response, which may be in part associated with the regulation of MMP-9 production and/or activation through the regulation of MMP-9 expression in mouse macrophage cells.

• BMB Reports
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• 제40권1호
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• pp.88-94
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• 2007

Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in the turnover of extracellular matrix (ECM) and in the migration of normal and tumor cells in response to normal physiologic and numerous pathologic conditions. Here, we show that the transcription of the MMP-9 gene is induced by lipopolysaccharide (LPS) stimulation in cells of a macrophage lineage (RAW 264.7 cells). We provide evidence that the NF-$\kappa$B binding site of the MMP-9 gene contributes to its expression in the LPS-signaling pathway, since mutation of NF-$\kappa$B binding site of MMP-9 promoter leads to a dramatic reduction in MMP-9 promoter activation. In addition, the degradation of l$\kappa$B$\alpha$;, and the presences of myeloid differentiation protein (MyD88) and tumor necrosis factor receptor-associated kinase 6 (TRAF6) were found to be required for LPS-activated MMP-9 expression. Chromatin immunoprecipitation (ChIP) assays showed that functional interaction between NF-$\kappa$B and the MMP-9 promoter element is necessary for LPS-activated MMP-9 induction in RAW 264.7 cells. In conclusion, our observations demonstrate that NF-$\kappa$B contributes to LPS-induced MMP-9 gene expression in a mouse macrophage cell line.

• 대한의생명과학회지
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• 제18권2호
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• pp.104-111
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• 2012

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which degrade extracellular matrix (ECM) during embryogenesis, wound healing, and tissue remodeling. Dysregulation of MMP activity is also associated with various pathological inflammatory conditions. In this study, we examined the expression pattern of MMPs during PMA-induced differentiation of THP-1 monocytic cells into macrophages. We found that MMP1, MMP8, MMP3, MMP10, MMP12, MMP19, MMP9, and MMP7 were upregulated during differentiation whereas MMP2 remained unchanged. Expression of MMPs increased in a time-dependent manner; MMP1, MMP8, MMP3, MMP10, and MMP12 increased beginning at 60 hr post PMA treatment whereas MMP19, MMP9, and MMP7 increased beginning at 24 hr post PMA treatment. To identify signal transduction pathways involved in PMA-induced upregulation of MMPs, we treated PMA-differentiated THP-1 cells with specific inhibitors for PKC, MEK1, NF-${\kappa}B$, PI3K, p38 MAPK and PLC. We found that inhibition of the MEK1 pathway blocked PMA-induced upregulation of all MMPs to varying degrees except for MMP-2. In addition, expression of select MMPs was inhibited by PI3K, p38 MAPK and PLC inhibitors. In conclusion, we show that of the MMPs examined, most MMPs were up-regulated during differentiation of monocyte into macrophage via the MEK1 pathway. These results provide basic information for studying MMPs expression during macrophage differentiation.

• 치위생과학회지
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• 제12권1호
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• pp.71-77
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• 2012

본 연구는 월경주기에 따른 치주조직의 변화에 관한 예비연구로, 건강한 치주조직을 가지고 있고 월경주기가 일정한 20대 여성 7명과 남성 3명을 대상으로 4주간 8회 추구조사를 하였다. 시진상 치주조직의 상태는 건강하므로 치은열구액 내 바이오마커의 변화를 기준 변수로 하여, 상악전치부 치은열구액 내 MMP-9과 MMP-8, IL-$1{\beta}$의 농도를 측정하여 비모수 검정방법으로 분석하였다. 그 결과, 1. 여성대상자에서 월경시기, 배란추정시기에 각 염증지표들이 상승하는 추세를 보였으나 변화정도는 유의하지 않았다. 2. 성별에 따른 각 염증지표들의 차이는 유의하지 않았으며, MMP-9, MMP-8의 농도는 차이가 없었으나 IL-$1{\beta}$의 농도가 남성에서 유의하게 높았다(p=0.03). 3. 검사시점별 각 염증지표들의 상관관계는 강하거나 상당한 강한 양적 선형관계를 나타내었고 배란추정 시기와 월경시기에 상관계수가 더 높게 나타났다. 4. MMP-8과 IL-$1{\beta}$의 관계는 모든 검사시점에서 유의하였으나 MMP-9의 경우, MMP-8과 IL-$1{\beta}$의 상관관계가 유의하지 않은 시점도 있었다. 따라서, 여성대상자도 월경주기에 따른 변화정도가 남성대상자와 유의한 차이가 없으므로 치주병 위험요인에 따른 치주조직 변화의 추구조사에 참여할 수 있는 근거가 마련되었다. 또한 검사지표 중에 MMP-8이 모든 시점에서 다른 지표와 유의하고 강한 상관관계를 나타내어 대표 바이오마커로 적합할 것으로 사료되었다.

• Natural Product Sciences
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• 제27권3호
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• pp.151-160
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• 2021

Under some pathological conditions such as osteoarthritis, matrix metalloproteinases (MMPs) including MMP-13 have an important role in degrading cartilage materials. When the regulatory effects of some herbal extracts on MMP-13 expression were examined to evaluate the cartilage-protective potential, the ethanol extract of the radix of Viscum album was found to strongly downregulate MMP-13 induction in IL-1β-treated chondrocytes, SW1353 cells. Based on this finding, activity-guided separation was carried out, which yielded five constituents identified as 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (1), hesperetin-7-glucoside (2), syringin (3), homoflavoyadorinin B (4), and 4,4'-dihydroxy-3,6'-dimethoxychalcone-2'-glucoside (5). Of these, 1 and 5 significantly inhibited MMP-13 expression in SW1353 cells, with 5 being the most potent. Compound 5, a chalcone derivative, showed the downregulation of MMP-13 at 20 - 100 μM. The mechanism study revealed that 5 exerted MMP-13 down-regulatory action, at least in part, by interrupting the signal transducer and activator of transcription 1 (STAT1) activation pathway. Furthermore, this compound protected against cartilage degradation in an IL-1-treated rabbit cartilage explant culture. All these findings demonstrated for the first time that Viscum album and its constituents, especially chalcone derivative (5), possessed cartilage-protective activity. These natural products may have the potential for alleviating cartilage degradation.

• 치위생과학회지
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• 제11권4호
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• pp.339-344
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• 2011

본 연구는 흡연군, 흡연중단군, 비흡연군의 치은열구액 내 MMP-9을 측정하여 흡연과 치은열구액 내 MMP-9의 관계를 조사하고자 2009년부터 9월부터 2010년 7월까지 본 연구에 동의한 332명을 대상으로 기초설문조사와 치면세균막지수, 치주낭측정 등을 실시하고 치은열구액을 상악전치부 치간 사이 채취하여 치은열구액 내 MMP-9의 농도를 측정하여 분석하였다. 그 결과, 1. 연령대에 따른 치은열구액 내 평균 MMP-9의 농도는 10대 7.54ng/ml, 20대 15.98 ng/ml, 30대 28.47ng/ml, 40대 36.78ng/ml, 50대 이상은 45.06ng/ml로 집단간의 차이는 유의하였다(p<0.001). 2. 치은지수에 따른 치은열구액 내 평균 MMP-9의 농도는 0점 16.15ng/ml, 1점 20.97ng/ml, 2점 48.79ng/ml로 치은지수가 증가함에 따라 치은열구액 내 MMP-9의 농도가 증가하는 경향을 보였으나 유의하지는 않았다(p>0.05). 3. CPI에 따른 치은열구액 내 평균 MMP-9의 농도는 0점 14.74ng/ml, 1점 6.57ng/ml, 2점 10.29ng/ml, 3점 29.71ng/ml, 4점 56.52ng/ml였으며 군간 유의한 차이가 있었다(p<0.001). 4. 흡연여부에 따른 치은열구액 내 MMP-9의 평균 농도는 흡연군이 30.86ng/ml, 흡연중단군이 29.82ng/ml, 11.33ng/ml이었으며 연령, 치은지수, CPI을 공변량으로 보정한 전, 후 모두에서 각 군간 유의한 차이를 나타내었다(p<0.001). 흡연, 흡연중단군이 비흡연군에 비해 치은열구액내 MMP-9의 농도가 높은 것으로 나타나 흡연은 치은열구액 내 MMP-9의 농도를 증가시키고 있는 것으로 보이며 MMP-9은 치조골 파괴 및 치주질환에 영향을 미치므로 흡연자에서 치주질환 발생 및 발생가능성이 높을 것으로 사료되었다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제29권4호
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• pp.212-218
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• 2003

Matrix metalloproteinases (MMPs) play an important role in the normal morphogenesis, maintenance, and repair of matrix and also have important functions in pathologic conditions characterized by excessive degradation of extracellular matrix, such as rheumatoid arthritis, osteoarthritis, periodontitis and in tumor invasion and metastasis. In this study, expression of MMP-1 and -2 mRNA in retrodiscal tissue of the temporomandibular joint (TMJ) was examined and compared with magnetic resonance imaging (MRI) and surgical findings. MMP mRNAs in the retrodiscal tissue samples were detected by reverse transcription - polymerase chain reaction. TMJ internal derangement (ID) was categorized as normal disc position, disc displacement with reduction, early stage of disc displacement without reduction (DDsR) and late stage of DDsR. TMJ osteoarthrosis (OA) was classified with normal, mild and advanced OA. The amount of synovial fluid collection was divided into not detected, small, large and extremely large amount on MR T2-weighted imaging. Perforation and adhesion were examined during open surgery of the TMJ. Six out of 37 samples were excluded because of little amount of extracted total mRNA. MMP-2 mRNA was detected whole joints, and so the MMP-2 mRNA seems to be expressed normally in retrodiscal tissue. However, MMP-1 mRNA was expressed in 8 of 31 joints. Frequencies of MMP-1 mRNA expression according to the TMJ IDs, amount of synovial fluid and surgical findings made no significant difference. MMP-1 mRNA was detected more frequently in OA groups (7/16 joints, 43.8%) than in normal bony structure group (1/15 joints, 6.7%). Expression of MMP-1 mRNA in retrodiscal tissue might be related with OA of the TMJ.