• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.167-180
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• 2017

Human adult stem cells have widely been examined for their clinical application including their wound healing effect in vivo. To function as therapeutic cells, however, cells must represent the ability of directed migration in response to signals. This study aimed to investigate the mechanism of platelet-derived growth factor (PDGF)-induced migration of the human abdominal adipose-derived stem cells (hADSCs) in vitro. A general matrix metalloproteinase (MMP) inhibitor or a MMP2 inhibitor significantly inhibited the PDGF-induced migration. PDGF treatment exhibited greater mRNA level and denser protein level of MMP1. The conditioned medium of PDGF-treated cells showed a caseinolytic activity of MMP1. Transfection of cells with siRNA against MMP1 significantly inhibited MMP1 expression, its caseinolytic activity, and cell migration following PDGF treatment. Phosphatidylinositol 3-kinase (PI3K) inhibitor reduced the migration by about 50% without affecting ERK and MLC proteins. Rho-associated protein kinase inhibitor mostly abolished the migration and MLC proteins. The results suggest that PDGF might signal hADSCs through PI3K, and MMP1 activity could play an important role in this PDGF-induced migration in vitro.

• Restorative Dentistry and Endodontics
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• 제46권3호
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• pp.36.1-36.11
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• 2021

Objectives: This study aimed to evaluate Emblica officinalis (Indian gooseberry or amla) as an acid etchant and matrix metalloproteinase (MMP) inhibitor, and to compare its effect on the microshear bond strength of composite resin with orthophosphoric acid (OPA) and 2% chlorhexidine (CHX) as an acid etchant and MMP inhibitor, respectively. Materials and Methods: The etching effect and MMP-inhibiting action of amla on dentin samples were confirmed by scanning electron microscopy (SEM) and gelatin zymography, respectively. Dentinal slabs (3 mm thick) from 80 extracted human molars were divided into 10 and 20 samples to form 2 control groups and 3 experimental groups. Groups 1, 2, and 4 were etched with OPA and groups 3 and 5 with amla juice. An MMP inhibitor was then applied: CHX for group 2 and amla extract for groups 4 and 5. Groups 1 and 3 received no MMP inhibitor. All specimens received a standardized bonding protocol and composite resin build-up, and were subjected to microshear bond strength testing. The force at which the fracture occurred was recorded and statistically analyzed. Results: Amla juice had a similar etching effect as a self-etch adhesive in SEM and 100% amla extract was found to inhibit MMP-9 by gelatin zymography. The microshear bond strength values of amla were lower than those obtained for OPA and CHX, but the difference was not statistically significant. Conclusions: Amla has a promising role as an acid etchant and MMP inhibitor, but further studies are necessary to substantiate its efficacy.

• BMB Reports
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• 제32권1호
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• pp.60-66
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• 1999

Matrix metalloproteinase-2 (MMP-2; 72-kDa gelatinase; 72-kDa type IV collagenase; gelatinase A) plays an important role in normal physiological processes and in many pathologic processes such as arthritis and metastasis of cancer. Tissue inhibitor of metalloproteinases-2 (TIMP-2) binds to proMMP-2 or mature MMP-2 at a 1:1 ratio and inhibits the catalytic activity of MMP-2. We demonstrated that the baculovirus/insect cell system does not have TIMP-2 activity. The human proMMP-2 free of TIMP-2 was expressed in the expression system and purified by one-step affinity chromatography using gelatin-Sepharose. The free proMMP-2 was autoactivated to the mature MMP-2 and autodegraded into smaller molecular weight forms in the absence of external activator. The activation and autodegradation of the proMMP-2 was much more rapid in the presence of 4-aminophenylmercuric acetate (APMA). Addition of TIMP-2 inhibits both APMA-induced activation and autodegradation of the free proMMP-2. However, an increasing concentration of TIMP-2 more readily inhibited activation of the free proMMP-2 than autodegradation. These results demonstrate that TIMP-2 plays roles in inhibition of both activation and autodegradation of the free proMMP-2 in addition to inhibition of the catalytic activity of MMP-2.

• Archives of Pharmacal Research
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• 제28권11호
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• pp.1257-1262
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• 2005

MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-$\alpha$ stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-$\alpha$ stimulation. To investigate the signaling pathway underlined in TNF-$\alpha$ induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-$\alpha$ treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-$\alpha$. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-$\alpha$ induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-$\alpha$. Taken together, we found that TNF-$\alpha$ stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.

• Journal of Chest Surgery
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• 제40권5호
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• pp.329-340
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• 2007

배경: Matrix metalloproteinase (MMP) 차단은 심근경색 후 좌심실 확장에 대한 가능한 치료 전략으로 대두되고 있다. 선택적 MMP 차단제의 투여가 심근경색 후 초기 단계에 MMP가 대량으로 분비되는 짧은 기간을 차단하는 것이 좋을 것인지, 초기 전체 기간 동안 차단하여야 할 것인지를 알아보고자 하였다. 대상 및 방법: 토끼를 이용하여 기관 삽관 하에 전신 마취를 하고 흉골 정중절개한 다음 좌전 하행지 관상동맥을 결찰하여 심근경색을 만들었다. 실험군은 3군으로 나누었다. 심근경색 단독(MI only 군)군은 7예, MMP 차단제 5일 투여군(MMPI 5d 군)은 6예, MMP 차단제 9일 투여군(MMPI 9d 군)은 5예이었다. MMP 차단제로는 MMP-2와 MMP-9에 대한 선택적 차단제인 CG2300을 사용하였다. 각 군은 심장초음파도 검사를 4회 시행하였는데, 술 전, 술 후 1주, 2주 및 3주에 하였다. 검사는 2D 심초음파도를 사용하여 EDD, ESD 및 EF를 측정하였다. 술 후 4주에 희생한 토끼의 심장을 western blotting과 zymography를 하여 MMP-2와 MMP-9의 단백질과 활성의 변화를 조사하였고, 경색부위를 병리학적 조직검사를 하였다. 결과: 심초음파도 검사상, MI only군에서는 대체로 술 전에 비하여 술 후 EDD와 ESD가 증가한 추세로 좌심실이 확장하였음을 알 수 있었다. MMP 차단제 9일 투여군에서는 심근경색 단독군과 MMP 차단제 5일 투여군에 비해 좌심실의 확장이 감소한 경향을 보였다. EF는 MMP 차단제 9일 투여군에서 술 후에 술 전과 큰 변동이 없었으며, 다른 군들보다 높은 경향이었다. MMP 단백질의 발현과 활성 변화를 보면, 심근경색 단독군, MMP 차단제 5일 및 9일 투여군 등 3군을 정상 심장군과 비교하였을 때 MMP-2 단백질 발현과 활성 변화는 일어나지 않았다. 그리고 MMP-9의 단백 발현 및 활성은 검출되지 않았다. 병리학적 조직 소견을 보면 심근경색 단독군에서 심한 교원질 침착이 있었다. MMP 차단제 5일 투여군과 9일 투여군에서는 교원질 축적이 감소된 경향을 보였다. MMP 9일 투여군에서는 모세혈관의 수가 증가한 것을 볼 수 있었다. 결론: 관상동맥을 결찰하여 심근경색을 유도하면 술 후 빠른 시간 내에 심실이 확장되며 MMP 차단제를 투여할 경우 심실의 확장이 완화됨을 알 수 있었다. MMP 차단제의 효과는 초기의 대부분 기간을 차단하는 것이 좋다고 생각된다. MMP 차단제가 혈관신생을 증가시켜 심실 재형성을 완화할 수 있는 것으로 분석된다.

• 생명과학회지
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• 제16권7호
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• pp.1229-1234
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• 2006

배지에 tetracycline이 없으면 사멸하는 평활근세포 (FADD-SMC)를 이용하여 metalloproteinase (MMP)와 사멸세포의 상관관계를 조사하였다. FADD-SMC를 tetracycline이 없는 배지에서 배양하는 경우 핵이 조각으로 잘라졌고 인산화한 p38과 ERK가 증가하고 MMP-9의 발현과 활성이 증가한 반면, cyclin D와 cyclin D의 발현은 감소하였다. 그리고 죽는 FADD-SMC에서 MMP-9의 발현은 immunofluorescen로 재확인하였다. MMP-9의 증가는 MAPK 억제제인 PD098059와 p38 MAPK 억제제인 SB203S80에 의하여 감소하였다. 그리고 MMP 억제제인 BB94는 FADD-SMC의 사멸을 감소시켰다.

• Journal of Ginseng Research
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• 제22권3호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.873-876
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• 2013

Our aim was to test the hypothesis that preoperative serum levels of matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) levels correlate with pathological features. Serum levels of MMP-7, and MMP-9 and TIMP-1 were determined in 90 bladder cancer patients and 40 healthy controls using an enzyme linked immunosorbent assay. Preoperative serum MMP-7 and MMP-9 levels were significantly higher in cancer patients than control groups (p<0.001). In contast, serum TIMP-1 levels were lower (p<0.001). Alteration in MMP-7, and MMP-9, and TIMP-1 production may contribute to tumor angiogenesis and be associated with clinic-pathological features.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.41-42
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• 2003

Matrix metalloproteinases (MMPs) inhibitors were screened from Metasequoia glyptostroboides and one potent inhibitor, dihydrohinokiflavone (DHHF), a biflavonoid, was selected. DHHF inhibited proliferation of HT1080, human fibrosarcoma cells in a dose-dependent manner. Noncytotoxic levels of DHHF dramatically decreased MMP-9 and MMP-2 production in unistimulated cells, but did not change the level of tissue inhibited of metalloproteinase (TIMP)-1, an inhibitor of MMP-9.(omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.143-143
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• 2003

The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. An endogenous inhibitor of MMP, tissue inhibitor of metalloprotease-2 (TIMP-2), has high specificity for MMP-2. An imbalance between MMP-2 and TIMP-2 causes the degradation of the extracellular matrix associated with pathological events including invasion, metastasis and angiogenesis.(omitted)