• Journal of Life Science
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• v.6 no.4
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• pp.286-292
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• 1996

Angiogenesis is a fundamental process by which new blood vessels are formed. It is essential in embryo development, and wound healing. Furthermore, malignant tumor growth and metastasis are also angiogenesis-dependent. In the catilage tissue, normal angiogenesis process is suppressed. In fact, it was reported that angiogenesis-inhibitory substances were isolated from the extracts of cow and shark catilage tissue. In order to isolate genes involved in the regulation of angiogenesis from a catilage fish, we constructed a shark cDNA library from Scylliohinus torazame. We then screened the library using hyman tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene as a probe. Among the 4 X 10$^{4}$ plaques screened, we isolated 2 positive clones (T-1, T-2). Restriction enzyme analysis revealed that the T-1 clone contains 0.8 kb cDNA insert, and the T-2 clone contains 1.2 kb and 2.2 kb inserts, respectively. Further DNA sequence analysis shows that the DNA sequence of the T-1 clone is 53% homologous to that of the human TIMP-1 gene.

• Clinical and Experimental Pediatrics
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• v.58 no.11
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• pp.415-420
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• 2015

Purpose: Bronchopulmonary dysplasia (BPD) is characterized by inflammation with proteolytic damage to the lung extracellular matrix. The results from previous studies are inconsistent regarding the role of proteinases and antiproteinases in the development of BPD. The aim of the present study was to investigate whether matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, and TIMP-1 levels in the serum of preterm infants at birth are related to the development of BPD. Methods: Serum was collected from 62 preterm infants at birth and analyzed for MMP-8, MMP-9, TIMP-2, and TIMP-1 by using enzyme-linked immunosorbent assay. MMPs and TIMPs were compared in BPD (n=24) and no BPD groups (n=38). Clinical predictors of BPD (sex, birth weight, gestational age, etc.) were assessed for both groups. The association between predictors and outcome, BPD, was assessed by using multivariate logistic regression. Results: Sex, birth weight, and mean gestational age were similar between the groups. BPD preterm infants had significantly lower TIMP-2 levels at birth compared with no BPD preterm infants ($138.1{\pm}23.0ng/mL$ vs. $171.8{\pm}44.1ng/mL$, P=0.027). No significant difference was observed in MMP-8, MMP-9, and TIMP-1 levels between the two groups. Multivariate logistic regression analysis indicated that the TIMP-2 levels were predictive of BPD after adjusting for sex, birth weight, gestational age, proteinuric preeclampsia, and intraventricular hemorrhage (${\beta}=-0.063$, P=0.041). Conclusion: Low TIMP-2 serum levels at birth may be associated with the subsequent development of BPD in preterm infants.

• Molecules and Cells
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• v.25 no.1
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• pp.105-111
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• 2008

Radiotherapy is an important treatment for many malignant tumors, but there are recent reports that radiation may increase the malignancy of cancer cells by stimulating expression of type IV collagenases. In this study, we examined changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein levels but not mRNA levels, whereas no significant changes were found in TIMP-1 and TIMP-2. The enhanced RECK protein levels were associated with an increase in MMP inhibitory activity. However, irradiation slightly but reproducibly increased the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells with transforming growth factor $(TGF)-{\beta}1$ led to a 2-fold increase in RECK protein levels. Transient transfection with Smad3 also increased RECK protein levels, but transfection with Smad7 markedly reduced them. Stable expression of Smad7 and treatment with SB431542, an inhibitor of $TGF-{\beta}$ receptor I kinase, abolished $TGF-{\beta}1$- and radiation-mediated effects on RECK. Furthermore, irradiation increased levels of phosphorylated Smad3. We conclude that radiation post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in part, via $TGF-{\beta}$ signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.

• Tuberculosis and Respiratory Diseases
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• v.65 no.1
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• pp.7-14
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• 2008

Background: Residual pleural thickening (RPT) is the most frequent complication of tuberculous pleurisy (TP), and this can happen despite of administering adequate anti-tuberculous (TB) therapy. Yet there was no definite relation between RPT and other variables. The aim of this study was to examine matrix metalloproteinases (MMPs) and the inhibitors of metalloproteinases (TIMPs) and to identify the factors that can predict the occurrence of RPT. Methods: The patients with newly-detected pleural effusions were prospectively enrolled in this study from January 2004 to June 2005. The levels of MMP-1, -2, -8 and -9, and TIMP-1 and -2 were determined in the serum and pleural fluid by ELISA. The residual pleural thickness was measured at the completion of treatment and at the point of the final follow-up with the chest X-ray films. Results: The study included 39 patients with pleural fluid (PF). Twenty-three had tuberculous effusion, 7 had parapneumonic effusion, 7 had malignant effusion and 2 had transudates. For the 17 patients who completed the anti-TB treatment among the 23 patients with TP, 7 (41%) had RPT and 10 (59%) did not. The level of PF TIMP-1 in the patients with RPT ($41,405.9{\pm}9,737.3ng/mL$) was significantly higher than that of those patients without RPT ($29,134.9{\pm}8,801.8$) at the completion of treatment (p=0.032). In 13 patients who were followed-up until a mean of $8{\pm}5$ months after treatment, 2 (15%) had RPT and 11 (85%) did not. The level of PF TIMP-2 in the patients with RPT ($34.4{\pm}6.5ng/mL$) was lower than that of those patients without RPT ($44.4{\pm}15.5$) at the point of the final follow-up (p=0.038). Conclusion: The residual pleural thickening in TP might be related to the TIMP-1 and TIMP-2 levels in the pleural fluid.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.44 no.3
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• pp.120-127
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• 2018

Objectives: The aim of this study was to reveal how collagenases (matrix metalloproteinase [MMP]-1, 8, 13) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are expressed in immunohistochemistry of retrodiscal tissue in temporomandibular joint disorder patients. Materials and Methods: This study was conducted on 39 patients who underwent discoplasty or discectomy. Immunohistochemical staining was undertaken and expression levels of MMP-1, 8, 13, and TIMP-1 were evaluated. The status of internal derangement of disc, osteoarthritis, and joint effusion were analyzed using magnetic resonance imaging (MRI). Disc status observed during operation was also categorized. Results: The more severe disc derangement was observed on MRI, the more increased expression of MMPs and TIMP-1 appeared. Regarding MMP-13 expression, 86.7% of late-stage disc displacement patients showed grade II or III. Expression level of MMPs or TIMP was not statistically significant associated with joint effusion level. In perforation and/or adhesion groups, all patients showed grade II or III expression of MMP-13. Once perforation occurred, MMP-13 showed increased expression with statistical significance. Conclusion: MMP-1 and MMP-13 expression seem to be related to progression of osteoarthritis whereas MMP-8 does not seem to have a specific role with regard to temporomandibular joint disorders. TIMP-1 is considered to be partly related to internal derangement rather than osteoarthritis, but it is not significant.

• Tuberculosis and Respiratory Diseases
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• v.61 no.5
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• pp.447-455
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• 2006

Background: MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects. Method: The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2, -9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay. Results: (1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue. Conclusions: These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be important factors in the irreversible fibrosis of the lung parenchyme.

• Preventive Nutrition and Food Science
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• v.14 no.1
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• pp.14-20
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• 2009

Matrix metalloproteinases (MMPs) are a group of zinc proteases that serve the function of breaking down extracellular matrix (ECM). The present study evaluated the role of N-acetylcysteine (NAC) on the increased deposition of ECM in hepatic and glomerular fibrosis caused by carbon tetrachloride ($CCl_4$). The activity of MMPs increased and the levels of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) decreased in the liver and kidney of $CCl_4$-treated rats. Rats treated with $CCl_4$ and NAC showed increased activities of MMPs and decreased levels of TIMP-1 and TIMP-2 in the liver and kidney. Treatment with NAC resulted in the effective degradation of ECM due to an increase in the activities of MMPs and a decrease in the levels of TIMPs.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.121-125
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• 2005

Objectives: To investigate the role of MMP-2 and TIMP-2 in the invasion and metastasis of thyroid papillary microcarcinomas. Materials and Methods: We performed immunohistochemical study on MMP-2 and its tissue inhibitor (TIMP-2) using tissue microarrays containing 2 cores of 40 microPTC and 8 non-neoplastic thyroid tissue. The expression intensity was semiquantitatively scored as -, ${\pm}$, +1, +2, and +3. Results: Both MMP-2 and TIMP-2 expression was observed in all tumors(100%) and in 1 of 8 non-neoplastic tissue(12.5%), and the positive staining was restricted to the epithelial cells. In 17 and 23 tumors with or without extrathyroid invasion, respectively, 8(47%) and 10(43%) cases showed moderate to strong(+23) positivity for MMP-2. TIMP-2 expression was moderate to strong in 13 cases(76%) and 16 cases(70%) in each group. In multifocal and solitary tumors, 3 of 6(50%) and 11 of 21(52%) cases showed moderate to strong MMP-2 expression, and 5/6(83%) and 15/21(71%) showed moderate to strong TIMP-2 expression. Conclusion: There is no relationship between MMP-2 or TIMP-2 expression and extrathyroid invasion or tumor multifocality in papillary microcarcinoma of the thyroid gland.

• Food Science of Animal Resources
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• v.35 no.2
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• pp.164-170
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• 2015

The objective of this study was to evaluated the photoprotective effects of porcine placenta extract (PPE) on ultraviolet B (UVB)-induced oxidative stress in human keratinocytes (HaCaT) to evaluate its functional activities as a skin food ingredient. PPE prepared by subcritical water extraction was termed SPE, and subsequently digested by enzymes to prepare E-SPE. Increased intracellular reactive oxygen species (ROS) levels (192.0%) induced by UVB were decreased by SPE and E-SPE. SPE had more effective ROS scavenging activity than E-SPE treatment. UVB treatment increased expression of tissue inhibitor of metalloproteinase 1 (TIMP-1), and this elevated expression was decreased by E-SPE treatment. High-dose treatment with E-SPE (50 and 100 µg/mL) reduced TIMP-1 expression levels of UVB-C (control) to 33.5 and 34.6%, respectively. In contrast, at low SPE doses (1 and 10 µg/mL), the treatment slightly decreased TIMP- 1 expression levels to 73.3% and 71.3% of UVB-C, respectively. In conclusion, the present study demonstrated the protective effect of SPE and E-SPE against UVB damage in keratinocytes via ROS scavenging, down-regulating MMP-2 expression and up-regulating TIMP- 1 expression. This highlights the potential for SPE as an ingredient in the preparation of functional food against photoaging.

• Tuberculosis and Respiratory Diseases
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• v.61 no.3
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• pp.256-264
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• 2006

Background: An acute lung injury(ALI) is characterized by the recruitment, activation, and apoptosis of inflammatory cells, numerous products released by inflammatory cells such as reactive oxygen species, inflammatory mediators, and a variety of proteolytic enzymes. It was reported that bacterial infections in diabetics showed impaired PMN functions such as reduced PMN respiratory burst and decreased microbicidal activity in inflamed tissue. However, the effect of the proteinase - inhibitor (MMP-9 vs TIMP-1) in ALI in diabetics is unclear. This study evaluated the differences in the expression of MMP-9 and TIMP-1 after the stimulation of endotoxin in a rat model. Methods: Six-week-old male Sprague-Dawley rats were classified into normal, DM, LPS and DM+LPS groups. The peripheral blood, BAL fluids, and lung tissues were obtained from individual rats. The MMP-9 activity was measured by gelatin zymography and the TIMP-1 level was measured by Western blotting. Results: The total BAL cells of the DM-LPS groups were significantly lower than the LPS groups (p < 0.01). The MMP-9 activities in the serum were higher in the DM+LPS groups than in the other groups. The MMP-9 activities in the BAL fluids were significantly higher in the DM+LPS group than in the normal and diabetic rats (p < 0.05). TIMP-1 expressions in the BAL fluids were significantly lower in the DM+LPS group than other groups (p < 0.05). The ratio between MMP-9 and TIMP-1 in the BAL fluids was significantly higher in the DM+LPS groups (p < 0.05). Conclusion: In ALI in diabetics the higher MMP-9 activity and lower TIMP-1 level are believed to prolonged and intensify the course of inflammation.