• Biomedical Science Letters
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• v.19 no.1
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• pp.9-16
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• 2013

Elevated blood triglyceride (TG) levels correlate with development of atherosclerosis suggesting that TG may promote the development of this disease. During atherosclerosis, TG is taken up by tissue macrophages which result in dramatic changes in various secreted factors. One such factor is the family of matrix metalloproteases (MMP) which are involved in tissue remodeling during both physiological and pathological processes. In this study, we examined the MMP expression profile in PMA-differentiated THP-1 macrophages treated with TG. We found that TG-treated THP-1 macrophages showed decreased expression of MMP-3, MMP-7, MMP-8 and MMP-9 in a time- and dose-dependent manner. In contrast, expression of MMP-1, MMP-2, and MMP-10 remained relatively unchanged after TG treatment. In addition, we found that expression of select MMPs was affected by various inhibitors of signaling pathways. In particular, expression of MMP-3 was slightly recovered by cRAF and PLC signaling pathway inhibitors. These data suggests a possible role of MMPs in macrophages during TG-induced atherosclerosis.

• Journal of Periodontal and Implant Science
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• v.37 no.sup2
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• pp.297-310
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• 2007

치조골 흡수는 파골세포와 matrix metalloproteinases (MMPs)에 의한 골의 무기질과 유기질의 파괴로 일어나는 과정이다. 세균성 산물, 주로 내독소는 치은조직 내에서 염증세포의 유주, 사이토카인 생산, 조직파괴 효소 분비 및 파골세포 활성 등의 국소 면역반응을 유도한다. A. actinomycetemcomitans는 급진성 치주염의 원인 균주중 하나로 그 내독소는 치조골의 흡수와 관련된다. MMP-13은 세균성 산물이나 염증성 사이토카인의 자극에 의해 분비되며, 최근의 연구 결과들은 MMP-13이 치주질환의 진행과 골 흡수 과정에서 일정한 역할을 담당하는 것으로 보고하고 있으나, A. actinomycetemcomitans 내독소와 MMP-13과의 관련성에 대한 연구는 미미하다. 이에 이번 연구에서는 A. actinomycetemcomitans 내독소에 의한 MMP-13의 발현과 파골세포 형성을 세포배양을 통하여 관찰하였고, 백서 구개부 치은에 A. actinomycetemcomitans 내독소를 주입하여 흡수가 진행되고 있는 치조골에서 파골세포의 분화와 MMP-13의 발현을 TRAP 염색, 면역조직화학적 방법 등을 통해 관찰하여 다음과 같은 결과를 얻었다. MMP-13 mPNA의 발현은 A. actinomycetemcomitans 내독소 (1ug/ml)로 24시간 자극한 마우스 치주인대 섬유모세포에서 생리식염수로 자극한 세포에 비하여 약 2.6배 증가하였으며 마우스 대식세포에서는 TRAP 양성 세포가 대조군보다 더 많이 나타났다. A. actinomycetemcomitans 내독소를 주입한 백서 치주조직에서는 대조군보다 더 심한 골소실을 보였다. TRAP-양성 다핵 파골세포 유사세포는 치주염군과 대조군 모두 치조골에서 관찰되었다. TRAP-양성 다핵 파골세포 유사세포는 치주염군에서 대조군보다 유의하게 많은 숫자가 관찰되었으며, 치주염군에서 대조군보다 유의하게 많은 숫자가 관찰되었다. MMP-13 면역양성 반응은 치주염군에서 거친 골연을 갖는 치조골상에 배열된 조골세포와 그 인접한 치주인대에서 관찰되었으며 대조군에서는 MMP-13 면역 양성 반응이 치조골 표면에서만 일부 관찰되었다. 이상의 결과는 A. actinomycetemcomitans 내독속가 MMP-13의 발현을 증가시키며 파골세포의 활성을 통하여 치조골의 흡수를 유도함을 시사한다. 또한 A. actinomycetemcomitans 내독소 투여에 의한 실험적 모델은 백서에서 중등도의 골 소실을 동반한 만성 치주염 모델로 향후 치주질환 치료제의 효과를 평가하는데 유용하게 사용될 수 있으리라 기대된다.

• Journal of Life Science
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• v.19 no.6
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• pp.836-838
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• 2009

Tissue plasminogen activator (tPA) is very useful for dissolving the clots of blood, however, the use of tPA is limited to only 3-5% of ischemic stroke patients because of the narrow therapeutic time windows and negative side effects. Previous evidences suggest that limitation of tPA in thrombolytic therapy may be related to the upregulation of MMPs. However, little is known about the regulatory mechanism. In this study, we examined the role of tPA on MMP upregulation in rat neuronal cells. tPA (5 ${\mu}g$/ml) increased MMP-9 levels of neuronal cells in a time dependent manner. Hypoxia/reoxygenation amplified tPA-induced MMP-9 levels significantly. Pretreatment with JNK inhibitor SP600125 reduced the MMP-9 response. These results suggest that tPA can upregulate MMPs in neuronal cells and that JNK kinase may be involved.

• Journal of Life Science
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• v.14 no.2
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• pp.263-268
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• 2004

The sprouting of vascular endothelial cells is an initial step in angiogenesis. Matrix metalloproteinases can associate with integrin on the surface of endothelial cells, thereby promoting angiogenesis. The purpose of this study was to test if fibroblast growth factor-2 (FGF-2) can regulate the sprouting in porcine pulmonary artery endothelial cells. FGF-2 induced sprouting and secretion of MMP-2 and plasmin. FGF-2 also induced the expression of integrin Mac-1, which is inhibited IS20I. Addition of BB-94, a 2-antiplasmin and IS20I inhibited FGF-2-induced sprouting activity. Therefore, FGF-2-induced sprouting activity in PPAECs may be accomplished by secretion of proteinases such as MMP-2 and plasmin and integrin expression.

• BMB Reports
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• v.40 no.1
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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.

• International Journal of Oral Biology
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• v.36 no.4
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• pp.195-201
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• 2011

Matrix metalloproteinases (MMPs) have been implicated in tissue development and re-modeling. Dynamic morphological changes of tooth germs reflect involvement of these enzymes during odontogenesis. The present study was performed to investigate expression and localization of MMP-2 and MMP-9, which have been known to have type IV collagenase activities, in rat tooth germs at different developmental stages. MMP-2 expression was increased gradually in the tooth germs from cap to crown staged germs at both transcription and translation levels. The localization of this molecule was detected in secretory ameloblasts and preameloblasts. The strong immunoreactivities were occasionally seen along the basement membrane between ameloblasts (or preameloblasts) and odontoblasts (preodontoblasts). However, weak reactivity was detected in odontoblasts and reduced enamel epithelium. The level of MMP-9 expression in the tooth germs was higher in cap stage than in crown staged germs at both transcription and translation levels. They were strongly expressed in both ameloblasts and odontoblasts. Even though reduced enamel epithelium after enamel formation and inner enamel epithelium at the cap stage exhibited weak reactivity, strong reactivity was detected in dental follicles and perifollicular tissues surrounding cap staged germs. These results suggested that MMP-2 may involve degradation of the basement membrane during hard tissue formation, whereas MMP-9 might be involved in remodeling of follicular tissues.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.277-288
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• 2005

There is a potential role of collagenase-3 in alveolar bone loss and periodontal disease progression, we need to develope or find chemotherapeutic drugs or herbal agents which may regulate the expression of MMP-13. Ginseng saponin, one of the major components of Korea ginseng(panax ginseng) root, has many various biologic effects, such as cytotoxic effect, tumoricidal effects, cytokine regulations, and protein biosynthesis effect. The purpose of this study was to determine the effects of Korea red ginseng saponin on MMP-13 gene expression in osteoblasts. The experimental groups were cultured with ginseng saponin in concentration of 1.0, 10, 25, 50, 100, 250 and $500{\mu}g/ml$ for MTT assay. Primary rat calvarial cells were pre-treated for 1 hour with ginseng saponin(100 ${\mu}g/ml$) and then stimulated with $IL-1{\beta}(1.0ng/ml)$ and PTH(10 nM). MMP-13 gene expression was evaluated by RT-PCR. The results were as follows: Ginseng saponin was cytotoxic to osteoblast at concentration exceeding $250{\mu}g/ml$ for longer than 24 hours in tissue culture(p<0.01). In RT-PCR analysis, steady state MMP-13 mRNA levels were increased approximately 350% by $IL-1{\beta}$, and 400% by PTH when normalized to untreated control. $IL-1{\beta}-indued$ MMP-13 mRNA expression was reduced 50% by pretreatment with ginseng saponin. But ginseng saponin didn't inhibit MMP-13 expression from PTH stimulated cells. This results suggest that ginseng saponin Inhibit $IL-1{\beta}-indued$ MMP-13 mRNA expression.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1229-1234
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• 2006

This study investigated whether matrix metalloproteinases (MMPs) can be modified in apoptotic smooth muscle cell (SMC) using the SMC that undergoes apoptotic death by expressing Fas-associated death domain containing protein (FADD) when they are grown without tetracycline in culture medium. In the absence of tetracycline, FADD-SMC lost adherence and showed the fragmentation of the nuclei. In proportion to duration of tetracycline removal, phosphorylated form of p38 MAPK and of ERK increased, whereas phosphorylation of protein kinase B (PKB) was not changed very much in response to tetracycline The levels of cyclin A and cyclin D were also decreased in a time dependent manner. Up-regulation of MMP-9 expression and activity was observed when the SMC were grown without tetracycline. Immunoreactivity of MMP-9 was detected from both attached and floating FADD-SMCs grown without tetracycline. An inhibitor of MAPK kinase, PD098059, and an inhibitor of p38 MAPK, SB203580, inhibited the up-regulation of MMP-9. Treatment of the SMC with a synthetic MMP inhibitor, BB94, attenuated death occurring in the absence of tetracycline. These results indicate that SMC undergoing death is able to up-regulate MMP-9 and that the enzyme can affect cell viability.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.483-491
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• 2021

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.4 s.48
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• pp.439-444
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• 2004

UV irradiation produces free radicals and related reactive oxygen species (ROS), and these are injury to all most of organisms of skin cells and extracellular matrix (ECM). In addition, free radicals and ROS stimulate the overexpression of matrix metalloproteinases (MMPs) that can degrade most components of ECM such as collagen. Since collagen constitutes almost of skin connective tissue, their disarrangement causes wrinkle formation and droop of skin. Therefore, scavenging activity on free radicals, ROS and suppression of MMP-1 is expected to prevent skin photoaging. In this study, to investigate the relationship between photoaging and Draconis sanguis, we examined the effects of antioxidant, in vitro MMP inhibition and expression of UVA-induced MMP-1 in human dermal fibroblasts. Draconis sanguis was found to show scavenging activities of radicals and ROS with the $IC_{50}$ values of $183{\;}{\mu}g/mL$ against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and $30{\;}{\mu}g/mL$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Draconis sunguis inhibited the activities of MMP-1 in a does-dependent manner and the $IC_{50}$ value calculated from semi-log plots was $200{\;}{\mu}g/mL$. Also, UVA induced MMP expression was reduced $74\%$ by treatment with Draconis sanguis, and MMP-1 mRNA expression was reduced in a dose-dependent manner. Therefore Draconis sanguis was able to significantly inhibit MMP expression in protein and mRNA level. All these results suggested that Draconis sanguis may act as an anti-photoaging agent by antioxidation and reducing UVA-induced MMP-1 production.