• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6749-6751
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• 2015

Background: Laryngeal cancer is an important malignancy in head and neck area and squamous cell carcinoma (SCC) is the most common type accounting for 95% of cases. Increase in matrix metalloproteinases (MMPs) in different tumors and their correlation with tumor invasiveness has been documented. However, most studies have evaluated MMP-2 and MMP-9 expression and few have evaluated serum levels. The aim of current study was to evaluate serum levels in patients with laryngeal SCC compared to normal subjects and assess any relation with tumor clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included. Serum levels of MMP-2 and MMP-9 were compared between groups and correlations with findings including grade (T) and node involvement (N) were evaluated. Results: Patients with laryngeal SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p=0.03) compared to healthy subjects. Patients with higher T stage (T3,4) had significantly higher MMP-2 (p=0.04) and MMP-9 (p=0.01). There was significant positive correlation between serum levels of MMP-2 with T stage (r=0.45, p=0.04) and lymph node involvement (r=0.563, p=0.01) and between levels of MMP-9 with T stage (r=0.527, p=0.01). Conclusions: Our results showed that compared to healthy subjects, both MMP-2 and MMP-9 are significantly increased in serum of laryngeal SCC cases. MMP-2 was correlated with lymph node involvement while MMP-9 has stronger correlation with T stage compared to MMP-2.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권3호
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• pp.137-145
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• 2009

As an efficient controlled release system for rhBMP-2, a functional nanoparticle-hydrogel complex, incorporated with matrix metalloproteinase(MMP) sensitive peptide cross-linker, was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase(ALP) activity and mineral contents analysis, based on the rat calvarial critical size defect(8mm in diameter) model. Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded MMP sensitive hyaluronic acid(HA) based hydrogel-Nanoparticles(NP) complex, as compared to only MMP HA, the MMP HA-NP without rhBMP-2, or even with the rhBMP-2. These improvements included the formation pattern of bone and functional marrow, the degree of calcium quantification, and the ALP activity. These results indicate that the MMP sensitive HA with nano-particle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced rhBMP-2 scaffold.

• International Journal of Oral Biology
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• 제40권3호
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• pp.127-133
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• 2015

The salivary gland undergoes complex process of growth and differentiation of the branching morphogenesis of ductal system during the prenatal and early postnatal periods which are regulated by various elements in the extracellular matrix. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell adhesion molecule. In the present study, localization and expression of EMMPRIN in development and effects of chorda-lingual denervation and cyclosporine A (CsA) treatment on the EMMPRIN expression were investigated. Immunohistochemistry, RT-PCR and Western blot were used to determine expression level. Immunohistochemistry revealed that EMMPRIN was localized specifically in the cytoplasm of ductal cells, not acini of the submandibular gland all the postnatal periods. At prenatal day 18, when the formation of ducts was not definite, no immunoreactivity was observed. Both Western blot and RT-PCR analyses revealed that EMMPRIN expression was maintained up to postnatal day 7, decreased after postnatal day 10. The EMMPRIN expression was upregulated by the surgical denervation of the chorda-lingual nerve in the gland as well as by the CsA treatment. The present study suggests that EMMPRIN is a crucial molecule for maintaining physiological functions of the salivary gland.

• 한국균학회지
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• 제45권3호
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• pp.175-187
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• 2017

Laetiporus sulphrueus var. miniatus is widely distributed worldwide, and has commonly been used as a medicinal mushroom. In the present study, we investigated the effects of water extract and solvent fractions from the Laetiporus miniatus as possible antioxidant, anti-thrombin and anti-invasive agents against phorbol 12-myristate 13-acetate (PMA)- or thrombin-induced matrix metalloproteinase-2 (MMP-2) and MMP-9 activities. Samples were fractionated into n-hexane, $CHCl_3$, ethyl acetate, n-butanol, and water fractions, and individually analysed. The water fraction had the highest extraction yield at 34.90% (w/w), while the n-butanol fraction demonstrated the highest anti-oxidative activity at 81.44%. In the thrombin inhibitory activity test, the water fraction exhibited the highest activity at 94.64%. Even at the concentration of $40{\mu}g/mL$, evaluation of anti-proliferating activity in YD-10B cells did not reveal any cytotoxic effects. Although MMP-9 expression in YD-10B cells increased after the addition of PMA and thrombin, MMP-2 did not. Additionally, MMP-2/-9 levels in PMA-treated YD-10B cells (i.e., both mRNA expression and protein activation) were highly inhibited in the hexane and chloroform fractions. Compared with MMP-2 levels, MMP-9 mRNA expression and proteolytic activity were inhibited to a greater extent by the hexane and chloroform fractions in thrombin-treated YD-10B cells. Taken together, these results support that thrombin induces tumor invasion through MMP-2/9 and suggest that the L. miniatus may act as an effective functional food, conferring anti-oxidative, anti-thrombotic and anti-cancer activities.

• 한국발생생물학회지:발생과생식
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• 제3권1호
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• pp.29-38
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• 1999

자궁내막증은 흔한 부인과적 질병이며 여성 불임의 한 원인이 되나 그 발생 원인에 대하여서는 아직 논란의 여지가 많다. 최근 월경혈의 역류가 한 원인이며 자궁내막증 환자가 정상여성에서 보다 역류되는 월경혈의 양이 많거나 침습성이 강한 것이 자궁내막증의 발생 원인이 될 수 있다는 이론들이 소개되었다. 종양이나 자궁내막 조직의 침습이나 전이에는 세포막외 기질 및 기저막의 파괴가 일어나야 하는데 이 과정에 plasminogen activators (PAs)나 matrix metalloproteinase (MMPs)같은 proteolytic enzyme이 관여한다. 이에 자궁 내막증환자와 대조군의 자궁내막에서 PA나 MMP를 억제하는 plasminogen activator inhibitor-1 (PAI-1)나 tissue inhibitor of metalloproteinase (TIMP-3)의 mRNA 발현의 차이를 quantitative competitive RT PCR로 연구하였으며, 그 결과 자궁내막증 환자의 황체기 자궁내막에서는 정상 대조군 환자에서 보다 PAI-1과 TIMP-3 mRNA발현이 낮음을 알 수 있었다. 따라서 자궁내막증 환자의 자궁내막에서는 PA와 MMP의 활성도가 증가할 수 있으며 이 증가된 proteolytic activity로 인하여 역류된 자궁내 막 조직의 복강내 침습이 보다 쉽게 일어날 가능성이 있다.

• Journal of Applied Biological Chemistry
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• 제65권4호
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• pp.277-286
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• 2022

Schizophragma hydrangeoides (S. hydrangeoides) is a vine endogenous to Jeju Island and Ulleungdo, where it grows attached to the foothills and rock surfaces. Previous research has mostly focused on the whitening effect of S. hydrangeoides leaf extract. In this study, we investigated S. hydrangeoides leaf extract further, and detected four phytochemicals in the extract: chlorogenic acid, quercetin-3-O-glucosyl-(1-2)-rhamnoside, quercetin-3-O-xylosyl-(1-2)-rhamnoside, and quercitrin. We pretreated human dermal fibroblast (HDFn) cells with previously established concentrations of the four compounds for 1 h before ultraviolet A (UVA) irradiation. Among the four compounds, quercetin-3-O-glucosyl-(1-2)-rhamnoside (Q-3-GR) best inhibited matrix metalloproteinase-1 (MMP-1) levels. Thus, we investigated the protective effects of Q-3-GR on photoaging and its underlying mechanisms. Q-3-GR significantly reduced MMP-1 production and inhibited MMP-1 protein expression in UVA-irradiated HDFn cells. Furthermore, Q-3-GR increased procollagen type I production and protein expression. Q-3-GR exerted its anti-photoaging effects by downregulating the mitogen-activated protein kinase/ activator protein-1 signaling pathway, and upregulating the transforming growth factor-β/Smad signaling pathway. Thus, S. hydrangeoides leaf-derived Q-3-GR is a potential potent cosmetic ingredient for UV-induced skin aging.

• 생명과학회지
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• 제16권3호
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• pp.442-446
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• 2006

참죽나무는 멀구슬과 나무로서 한국과 중국에 널리 분포하고 있다. 한방에서는 장염(腸炎), 이질(痢疾), 개선(疥癬) 등의 치료에 이용되고 있다. 본 연구는 참죽나무 잎에서 3종의 flavonol glycosides를 분리하여 NMR을 통해 구조를 확인한 결과, kaempferol-3-O-rhamnoside (1), quercetin-3-O-rhamnoside (2)와 quercetin-3-O-glucoside(3)로 구조 동정되었다. 분리된 화합물들의 생리활성은 matrix metalloproteinase-2 저해 활성과 인체암 세포주에 대한 세포독성과 apoptosis실험을 통하여 항암효과를 조사하였다. 그 결과 인체암 세포주에 대한 세포독성과 apoptosis 저해활성은 나타내지 않았으나, MMP-2활성저해 조사에서는 강한 저해 효과를 나타내었다. 특히 quercetin-3-O-glucoside는 암세포에 직접적인 독성을 보이는 것이 아니라 암의 침윤과 전이에 특이적으로 작용하는 물질로 보여진다.

• Journal of Korean Neurosurgical Society
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• 제40권5호
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• pp.363-368
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• 2006

Objective : Little is known about the comprehensive molecular and biological mechanism on the development of the degeneration of the intervertebral disc. Many kinds of matrix metalloproteinase[MMP] initiate the degradation of the extracellular matrix including several kinds of collagens and proteoglycans. We compared molecular and immunohistochemical features of degenerated intervertebral disc and normal counterparts in order to investigate the role of MMP-1, 2, 3, 9. Methods : We have evaluated MMP-1, 2, 3, 9 expression in 30 surgically resected lumbar disc from degenerative disc disease patients and 5 normal control cases. RT-PCR[reverse transcriptase-polymerase chain reaction] and immunohistochemistry were performed. Results : By RT-PCR, normal tissue samples showed merely scant expression of MMP-1, 2, 3, 9 mRNA, but degenerated disc samples revealed more pronounced expression. mRNA amplifications were detected in 60%, 63.3%, 70%, 53.3% cases By immunohistochemistry, normal tissue samples showed minimal protein expression of MMP-1, 2, 3, 9, but degenerated disc samples revealed more pronounced expression. Protein expressions were detected in 73.3%, 63.3%, 76.7%, 63.3% cases. Both the mRNA amplification and protein overexpression rates were significantly higher in degenerated disc than in the normal tissue. Concordance between both the mRNA amplification and protein expressions of MMP-1, 3, 9 were not observed, but there is well correlation in MMP-2 expression. Conclusion : We concluded that the over-expressions of the MMP-1, 2, 3, 9 may contribute to the development of degeneration of the intervertebral disc.

• Journal of Periodontal and Implant Science
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• 제36권2호
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• pp.409-425
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• 2006

치주질환의 병원균은 세포벽의 항원에 의하여 조직내 존재하는 mononuclear phagocytes가 활성화되어 cytokine들이 생성됨 으로써 치주 결체조직의 파괴를 진행시킨다. 이런 관련된 cytokine들은 순차적으로 상주하는 치은세포 및 대식세포가 Matrix metalloproteinase 합성을 하도록 유도하여 조직파괴를 시작한다. 이들 Matrix metalloproteinase중 MMP-2, MMP-9 (Gelatinase A,B)는 type IV collagen 및 변성된 interstitial collagen을 파괴하며 치주환자의 치은 열구액, 치은조직, 타액 네에서 높게 보고 되어왔다. 당뇨병은 치주질환의 위험요소중 하나로 달뇨 환자에서는 치주질환의 유병율이 일반인에 비해 높고 치주질환의 중증도도 더 심하여 진행도 빠르다고 알려져 있다. 그 병리 기전 중 하나로는 당뇨 환자에서는 치은 열구액 내 중성구 유래의 Matrix metalloproteinase의 활성 증가 및$TNF-{\alpha}$ 의 활성 증가가 추정되고 있다. 본 실험에서는 제2형 당뇨병 환자와 비당뇨 환자들에서 만성 치주염 부위의 치은 및 건강한 치은에서 염증매개체 중 하나인 MMP-2, MMP-9 및 $TNF-{\alpha}$ 의 발현에 대해 상호 비교 분석함으로서 염증, 혈당이 미치는 영향을 밝히고 제 2형 당뇨병 환자에서 심한 치주조직 파괴의 기전을 연구하고자 하였다. 경북대학교병원 치주과 내원환자 중 제2형 당뇨병 환자와 비당뇨 환자들 및 치주질환이 없는 건강인 대조군을 대상으로 여러 가지 환자요소, 임상 치주상태를 기록하고, 전신적으로 건강한 환자의 건강한 부위(n=8,Group 1), 전신적으로 건강한 환자으 만성 치주염 부위(n=8, Group 2), 제2형 당뇨병 환자의 만성 치주염 부위 (n=8,Group 3)에서 각각 변연치은을 채득하고 액화질소에 급속 동결하였다. Western blotting을 이용하여 각 조직 내 MMP-2, MMP-9 및 $TNF-{\alpha}$ 의 발현을 관찰, densitometer를 이용하여 상대적 발현을 정량, 각 조직의${\beta}-actin$을 이용하여 표준화하여 실험군과 대조군들의 평균치를 비교하였다. 비당뇨 환자들의 만성 치주염 부위 및 제2형 당뇨병 환자의 만성 치주염 부위에서 모두 건강 대조군에 비해 MMP-2와 MMP-9 의 발현이 증가되었다. 또한 MMP-2와 MMP-9는 2형 당뇨 환자의 만성 치주염 부위가 비당뇨 환자의 만성 치주염 부위보다 증가된 발현양상을 보였으며, $TNF-{\alpha}$ 발현 비교시 각 군간 유의성 있는 변화는 없었으나 2형 당뇨환자군에서 MMP-2 및 MMP-9의 증가와 함께 다소 증가 양상을 보였다. 결론적으로 본 실험에서 MMP-2 및 MMP-9의 증가가 만성 치주염 및 2형 당뇨 환자에서의 만성치주염에서 비당뇨환자 보다 MMP-2, MMP-9의 증가양상을 보여 주었으며 $TNF-{\alpha}$ 가 2형 당뇨환자의 만성치주염 진행과정에 기여인자로써 역할을 하는 것으로 생각된다.

• Journal of Periodontal and Implant Science
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• 제41권3호
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• pp.109-116
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• 2011

Purpose: The purpose of this study was to compare and quantify the expression of C-reactive protein (CRP), matrix metalloproteinase (MMP)-14, and tissue inhibitor of metalioproteinases (TIMP)-2 in gingival tissues of patients with chronic periodontitis accompanied with inflammatory reaction related to alveolar bone resorption with or without type 2 diabetes mellitus (DM). Methods: Twelve patients with type 2 DM and chronic periodontitis (group 3), twelve patients with chronic periodontitis (group 2), and twelve healthy individuals (group 1) were included in the study. Gingival tissue biopsies were collected from each patient and from healthy individuals at the time of periodontal surgery (including surgical crown lengthening) or tooth extraction. The concentrations of cytokines were determined by a western blot analysis. Results: The expression levels of CRP and MMP-14 increased in group 2 and 3, and they were highest in group 3. The expressions of TIMP-2 also increased in group 2 and 3. Conclusions: This study demonstrated that the expression levels of CRP, MMP-14, and TIMP-2 might be inflammatory markers in periodontal inflamed tissue. It can be assumed that CRP, MMP-14, and TIMP-2 may be partly involved in the progression of periodontal inflammation associated to type 2 DM.