• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.142-142
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• 2003

TGF-$\beta$ super family는 난소를 포함하여 여러 기관 및 조직의 성장에 광범위하게 영향을 미치는 것으로 알려져 있으며, TGF-$\beta$ super family는 난자의 매우 초기에 영향을 미치며, 난포의 성장을 촉진하여 초기의 난자의 형태를 이루는데 중요한 역할을 하는 것으로 알려져 있다. 한편 TIMP-1은 난관상피세포로부터 분비되는 난자의 생리활성 촉진인자로 보고되고 있다. 따라서 본 연구는 한우난포란의 체외성숙에 난자의 생리활성 촉진인자를 이용하여 한우 체외성숙 및 체외수정에 미치는 영향을 구명하고자 실시하였다. 한우 난포란은 도축암소의 난소를 채취하여 회수하였으며, 체외성숙은 HP-TCM를 기본 배양액으로 TGF-$\beta$ 0.1, 1, 10 ng/ml를 첨가하여 실시하였고, TIMP-1은 0.05, 0.5, 5ng/ml를 첨가하여 6, 12, 24시간 동안 체외성숙시켰다. 체외성숙된 난자는 체외성숙율을 검사하기 위하여, 0.1% aceto-orcein으로 염색을 실시하여 핵의 변화를 검사하였다. (중략)

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.4
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• pp.405-411
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• 2008

Purpose : Cyclosporine A (CsA) is a versatile immunosuppresive agent used to prevent graft rejection syndrome and treat autoimmune disease. One of the major side effects associated with CsA is the abnormal gingival hyperplasia. The purpose of this study was to investigate the relationship between the mRNA expression of the MMP-1, TIMP-1, and $TGF-{\beta}_1$ and the concentration of CsA in cultured human gingival keratinocytes. Materials & Methods : Gingival keratocytes were obtained from gingival tissues of 4 healthy donors. The cultured gingival keratocytes were incubated with increasing concentrations of CsA (0-2000 ng/ml) for 24 hours and the expression of MMP-1, TIMP-1, and $TGF-{\beta}_1$ were determined by reverse transcription-polymerase chain reaction (RT-PCR). Results : The expressions of MMP-1 and $TGF-{\beta}_1$ were not significantly different according to the concentrations of CsA. The expression of TIMP-1 was significantly increased at the CsA concentration of 500 ng/ml. Conclusion : We concluded that the gingival hyperplasia induced by CsA was more related with TIMP-1 than MMP-1 or $TGF-{\beta}_1$ on gingival collagen metabolism in patients treated with CsA.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.5
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• pp.445-453
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• 2006

Cyclosporine A (CsA) is a powerful immunosuppresive agent used to prevent graft rejection of organ and treat autoimmune disease. One of the major side effects associated with CsA treatment is the development of gingival overgrowth. The purpose of this study was to investigate the mRNA expression and association of the several growth factors in gingival overgrowth induced by CsA, respectively. Gingival fibroblasts were obtained from gingival tissues of healthy donor and the patients treated with CsA. The cultured gingival fibroblasts were incubated with increasing concentrations of CsA for 24 hours, and the expression of MMP-1, TIMP-1, $TGF-{\beta}_1$, p21 were determined by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of MMP-1 was slightly increased according to the concentration of treated CsA, but there was no statistical significance. TIMP-1 showed the increased expression at the CsA concentration of 250 and 500 ng/ml and significantly decreased at the CsA concentration of 750ng/ml. $TGF-{\beta}_1$ showed the increased expression at the CsA concentration of 500 and 750 ng/ml. The expression of p21 was not changed significantly. We concluded that the gingival hyperplasia induced by CsA was more related with $TGF-{\beta}_1$ than MMP-1 or TIMP-1 on gingival collagen metabolism in patients treated with CsA.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2003.10a
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• pp.142-142
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• 2003

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.5
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• pp.438-445
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• 2005

Cyclosporine A(CsA) is a powerful immunossuppresive agent used to prevent graft rejection of organ and treat autoimmune disease. One of the major side effects associated with CsA treatment is the development of gingival overgrowth. The purpose of this study was to evaluate the expression and association of the several growth factors in gingival overgrowth induced CsA using by immunohistochemical technique. Normal tissues as control were obtained from healthy normal gingivae and overgrowth gingival tissues as experiments were obtained from the patients taken the CsA. The expressions of the MMP-1, TIMP-1, TGF$\beta$-1, p21, p53, PCNA were evaluated by immunohistochemical technique. The more overgrowth was detected at the epithelial and connective tissue area in experimental group. The MMP-1, TGF$\beta$-1, p21, p53, PCNA expressions were significantly increased in experimental group. The TIMP-1 expressions was not significantly increased in experimental group. We could conclude that the gingival overgrowth induced CsA was related with the collagen matabolism in connective tissue and also the production of the growth factor from epithelial tissue.

• Preventive Nutrition and Food Science
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• v.18 no.2
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• pp.124-132
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• 2013

In this study, novel peptides (NIPP-1, NIPP-2) derived from Navicula incerta (microalgae) protein hydrolysate were explored for their inhibitory effects on collagen release in hepatic fibrosis with the investigation of its underlying mechanism of action. TGF-${\beta}1$ activated fibrosis in LX-2 cells was examined in the presence or absence of purified peptides NIPP-1 and NIPP-2. Besides the mechanisms of liver cell injury, protective effects of NIPP-1 and NIPP-2 were studied to show the protective mechanism against TGF-${\beta}1$ stimulated fibrogenesis. Our results showed that the core protein of NIPP-1 peptide prevented fibril formation of type I collagen, elevated the MMP level and inhibited TIMP production in a dose-dependent manner. The treatment of NIPP-1 and NIPP-2 on TGF-${\beta}1$ induced LX-2 cells alleviated hepatic fibrosis. Moreover, ${\alpha}$-SMA, TIMPs, collagen and PDGF in the NIPP-1 treated groups were significantly decreased. Therefore, it could be suggested that NIPP-1 has potential to be used in anti-fibrosis treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2087-2093
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• 2012

Previous evidence showed ${\beta}1$, 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of ${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in ${\beta}3GnT8$. Here we showed that cell proliferation was increased in ${\beta}3GnT8$ overexpressed cells but decreased in ${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in ${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of ${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$), whereas ${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of ${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the ${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.504-518
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect of greater celandine on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells (HSC-T6) were treated with various concentrations of greater celandine extract for 24, 48, and 72 hours. The extraction was done with distilled water. After the treatment, cell viability, proliferation, mRNA of the ${\alpha}SMA$, TIMP-1, TIMP-2, collagen I ${\alpha}$ 1, MMP-2, IL-6, TGF-${\beta}1$, PDGFr-${\beta}1$, Bcl-2, Bax, Bcl-xl, caspase-3, caspase-9 and the activities of SOD and catalase were measured by using MTT assay, BrdU assay, real-time PCR, superoxide dismutase assay and catalase assay. Results : The viability, proliferation, mRNA expression and synthesis of collagen of the hepatic stellate cells were inhibited as the concentration increased, which indicates the herb has an inhibitory effect on fibrogenesis of the liver by regulating the fibrosis associated genes in transcription. Conclusions : These results suggest that greater celandine would be beneficial in the treatment of fibrotic patients as well as for patients with chronic hepatitis.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.181-189
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• 2001

Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.