1.Altered expression of matrix metalloproteinases and tight junction proteins in rats following PEMF-induced BBB permeability change.
Ya Mei ZHANG ; Yan ZHOU ; Lian Bo QIU ; Gui Rong DING ; Xiao Feng PANG
Biomedical and Environmental Sciences 2012;25(2):197-202
OBJECTIVETo investigate the expression of occludin, ZO-1, MMP-2, and MMP-9 in cerebral microvasculature following Pulse Electromagnetic Field (PEMF) induced BBB permeability change.
METHODSSprague-Dawley rats were randomized into PEMF and sham exposed groups (n = 8). After exposure to PEMF at 0.5, 1, 3, 6, and 12 h, BBB permeability was measured by Evans-Blue extravasation. The expression of occludin, ZO-1, MMP-2, and MMP-9 were detected by real-time quantitative reverse transcriptase PCR and western blotting. MMP-2 and MMP-9 activity were detected by EnzChek gelatinase assay.
RESULTSCompared with the sham group, PEMF exposure led to increased permeability of the BBB to EB, which was prolonged after exposure. BBB permeability became progressively more severe, and recovered at 6 h. The gene and protein expression of occludin and ZO-1 were significantly decreased, while MMP-2 and MMP-9 expression were significantly increased after exposure to PEMF. All levels of expression recovered 12 h following PEMF.
CONCLUSIONChanges to BBB permeability were related to the alteration expression of tight junction proteins and matrix metalloproteinase after exposure to PEMF.
Animals ; Blood-Brain Barrier ; Electromagnetic Fields ; Male ; Matrix Metalloproteinases ; metabolism ; Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tight Junctions ; metabolism
2.The Expression of Matrix Metalloproteinases (MMPs), Tissue Inhibitor of Metalloproteinases (TIMPs) and Angiogenesis in Relation to the Depth of Tumor Invasion and Lymph Node Metastasis in Submucosally Invasive Colorectal Carcinoma.
Sung Ae JUNG ; Suk Kyun YANG ; Jeong Sun KIM ; Ki Nam SHIM ; Seock Ah IM ; Seung Jae MYUNG ; Hwoon Yong JUNG ; Chang Sik YU ; Jin Cheon KIM ; Weon Seon HONG ; Jin Ho KIM ; Young Il MIN
The Korean Journal of Gastroenterology 2005;45(6):401-408
BACKGROUND/AIMS: Lymph node (LN) metastasis occurs in approximately 10% of patients with submucosally invasive colorectal carcinoma. This study was performed to determine the role of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) production and microvessel formation on the LN metastasis in submucosally invasive colorectal carcinoma. METHODS: A total of forty-one subjects with surgically resected submucosally invasive colorectal carcinoma were included in this study. Immunohistochemical staining of MMP-2, MMP-9, TIMP-1, TIMP-2, and urokinase-type plasminogen activator were performed. Angiogenesis was evaluated by counting the number of microvessels in each pathologic specimen as identified by CD34 immunohistochemical staining. RESULTS: The depth of submucosal invasion was not significantly correlated with the expression of MMP-2, MMP-9, TIMP-1, TIMP-2, or urokinase-type plasminogen activator, but the microvessel count was significantly correlated with the absolute depth of invasion (r=0.312, p<0.05). Upregulation of TIMP-2 was positively correlated with adjacent lymphatic invasion (p<0.05) and increased TIMP-2 expression was correlated with LN metastasis in submucosally invasive colorectal carcinoma (p=0.088). CONCLUSIONS: These results suggest that the expression of TIMP-2 and the microvessel count may be useful parameters for considering additional surgery after endoscopic treatment of submucosally invasive colorectal carcinoma.
Adult
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Aged
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Aged, 80 and over
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Colorectal Neoplasms/blood supply/*metabolism/pathology
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Female
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Humans
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Immunohistochemistry
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Lymphatic Metastasis
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Male
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Matrix Metalloproteinases/*metabolism
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Middle Aged
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Neoplasm Invasiveness
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Neovascularization, Pathologic/*pathology
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Tissue Inhibitor of Metalloproteinases/*metabolism
3.Advances of vasculogenic mimicry in tumors.
Chinese Journal of Pathology 2007;36(10):694-697
Angiogenesis Inhibitors
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pharmacology
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Angiostatins
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pharmacology
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Animals
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Antigens, CD
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metabolism
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Cadherins
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metabolism
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Humans
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Matrix Metalloproteinase Inhibitors
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Matrix Metalloproteinases
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metabolism
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Microvessels
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metabolism
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Neoplasms
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blood supply
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pathology
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Neovascularization, Pathologic
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metabolism
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pathology
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Vascular Endothelial Growth Factor A
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metabolism
4.Effect of Erzhi Pill (二至丸) on improving cerebral nerve cell apoptosis in aging rats.
Hui-li GAO ; Dan-qiao WANG ; Xiao-yan WANG ; Zhi-guo WANG ; Xiang-ming WANG ; Zhao-en WU ; Hong LIU ; Yan-yan MA ; Xiao-hong NIU ; Lian-da LI
Chinese journal of integrative medicine 2010;16(6):504-509
OBJECTIVETo investigate the effects of Erzhi Pill (二至丸,EZP) on nerve cell apoptosis in senescence model rats.
METHODSThe rats model of senescence was established by peritoneal D-galactose injection combined with thymusectomy. Forty SD rats were randomized into four groups, the normal control group, the senescence model group, the EZP treated group, and the vitamins treated group, 10 in each group. The rats were made into senescence model except those in the normal group. In the same time of D-galactose injection, the rats were treated respectively with distilled water, EZP 4.32 g/kg, and vitamins E and C 0.06 g/kg daily for 6 weeks via intragastric infusion. The index of main viscera (as brain, testis, etc.), serum levels of superoxide dismutase (SOD) activity, and total anti-oxidation capacity (T-AOC) were measured after a 6-week treatment. Meanwhile, the cerebral cortex neuronal apoptosis proportion and mitochondrial membrane potential (MMP) were detected by flow cytometry.
RESULTSBoth EZP and vitamins E and C treatments showed effects on increasing testis index and serum level of T-AOC, reducing the percentage of neuronal apoptosis in the cerebral cortex, and elevating MMP in the aging rats model.
CONCLUSIONSEZP could inhibit the cerebral cortex neuron apoptosis and maintain the mitochondrial function in the senescent process of rats induced by peritoneal D-galactose injection combined with thymusectomy. It also shows antioxidation effect to some extents.
Aging ; blood ; drug effects ; Animals ; Antioxidants ; metabolism ; Apoptosis ; drug effects ; Cerebral Cortex ; cytology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Matrix Metalloproteinases ; metabolism ; Neurons ; cytology ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood
5.Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis.
Dong Hoon YU ; Jun Koo YI ; Hyung Soo YUH ; Seo jin PARK ; Hei Jung KIM ; Ki Beom BAE ; Young Rae JI ; Na Ri KIM ; Si Jun PARK ; Do Hyung KIM ; Sung Hyun KIM ; Myoung Ok KIM ; Jeong Woong LEE ; Zae Young RYOO
Experimental & Molecular Medicine 2012;44(9):529-535
Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular-superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC-SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1beta, TNFalpha, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.
Animals
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Arthritis, Experimental/blood/*enzymology/metabolism
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*Arthritis, Rheumatoid/enzymology/pathology
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Fibroblasts/metabolism
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Gene Expression Regulation
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Inflammation/pathology
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Interleukin-1beta/blood/metabolism
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Joints/enzymology/pathology
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Matrix Metalloproteinases/blood/metabolism
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Mice
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Mice, Transgenic
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Reactive Oxygen Species/metabolism
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*Superoxide Dismutase/genetics/metabolism
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Synovial Fluid/*enzymology
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Synovial Membrane/pathology
6.Effects of the knockdown of hypoxia inducible factor-1alpha expression by adenovirus-mediated shRNA on angiogenesis and tumor growth in hepatocellular carcinoma cell lines.
Sung Hoon CHOI ; Hye Won SHIN ; Jun Yong PARK ; Ji Young YOO ; Do Young KIM ; Weon Sang RO ; Chae Ok YUN ; Kwang Hyub HAN
The Korean Journal of Hepatology 2010;16(3):280-287
BACKGROUND/AIMS: Hypoxia-inducible factor-1alpha (HIF-1alpha) is a central transcriptional factor involved in the cellular responses related to various aspects of cancer biology, including proliferation, survival, and angiogenesis, and the metabolism of the extracellular matrix in hypoxia. This study evaluated whether adenovirus-mediated small hairpin RNA (shRNA) against HIF-1alpha (shHIF-1alpha) inhibits cell proliferation and angiogenesis in hepatocellular carcinoma (HCC) cell lines. METHODS: Knockdown of HIF-1alpha expression was constructed by adenovirus-mediated RNA interference tools, and HCC cell lines infected with shHIF-1alpha coding virus were cultured under a hypoxia condition (1% O2) for 24 hours. Following infection, the expression levels of HIF-1alpha, angiogenesis factors, and matrix metalloproteinase (MMP) were examined using Western blotting. Cell proliferation and angiogenesis were measured by a cell proliferation assay (MTT assay) and an angiogenesis-related assay (invasion and tube-formation assay), respectively. RESULTS: Adenovirus mediated inhibition of HIF-1alpha induced suppression of tumor growth in HCC cell lines. It also down-regulated the expression of angiogenesis factor and MMP proteins. Angiogenesis as well as mobility of vascular cells to tumor was suppressed by adenovirus-mediated shHIF-1alpha-infected groups in human umbilical vein endothelial cells (HUVECs). CONCLUSIONS: These data suggest that adenovirus-mediated inhibition of HIF-1alpha inhibits the invasion, tube formation, and cell growth in HUVECs and HCC cells.
Adenoviridae/genetics
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Carcinoma, Hepatocellular/*blood supply/metabolism/therapy
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Cell Line, Tumor
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Cell Proliferation
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Endothelial Cells/metabolism
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Gene Knockdown Techniques
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Genetic Vectors
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists &
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Liver Neoplasms/*blood supply/metabolism/therapy
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Matrix Metalloproteinases/metabolism
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Neovascularization, Pathologic/genetics/metabolism/*therapy
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RNA Interference
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RNA, Small Interfering/metabolism
7.Effect of anti-fibrosis compound contained serum on procollagen Type I and IV, matrix metalloproteinase and its tissue inhibitor-1 gene expression in HSC-LI90 cell line.
Gang ZHAO ; Ling-tai WANG ; Jian-jie CHEN
Chinese Journal of Integrated Traditional and Western Medicine 2004;24(1):47-50
OBJECTIVETo study the effects of Anti-fibrosis Compound contained serum (AFCS) on procollagen type I and IV (ProC-I and ProC-IV), matrix metalloproteinase (MMP) and its tissue inhibitor (TIMP-1) gene expression in hepatic stellate cell line LI90 (HSC-LI90).
METHODSAFCS was prepared by gastric infusing different dosage (0.5 g/kg, 2.0 g/kg and 4.0 g/kg) of Anti-fibrosis Compound Recipe to rats. After HSC-LI90 cells were exposed to AFCS for 48 hrs, levels of ProC-I, ProC-IV, gene expression of MMP-2, MMP membrane type 1 (MT1-MMP) and TIMP-1 in the cells were detected by Northern blot, and gelatinase activity of MMP-2 was measured by zymography.
RESULTSAFCS of different concentrations could inhibit ProC-I and ProC-IV and TIMP-1 gene expression (P < 0.05 or P < 0.01), increase MT1-MMP gene expression (P < 0.01), but it showed no effect on gene expression and activity of MMP-2 (P > 0.05).
CONCLUSIONAnti-fibrosis Compound Recipe has anti-liver fibrosis action, its effects in inhibiting TIMP-1 gene expression of HSC-LI90 cells and promoting degradation of collagen might be one of the mechanisms of the action.
Animals ; Cell Line ; Collagen Type I ; biosynthesis ; genetics ; Collagen Type IV ; biosynthesis ; genetics ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression ; Hepatocytes ; metabolism ; pathology ; Liver Cirrhosis ; blood ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinases ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Serum ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics
8.Differential expression of a homing-related molecule repertoire among umbilical cord blood, mobilized peripheral blood and bone marrow-derived hematopoietic stem/progenitor cells.
Yi-zhou ZHENG ; Li ZHANG ; Hui-jun WANG ; Zhong-chao HAN ; Tsuneo A TAKAHASHI
Chinese Journal of Hematology 2004;25(12):736-739
OBJECTIVETo compare the expression profiles of a set of homing-related molecules (HRM) repertoire expressed on hematopoietic stem/progenitor cells (HS/PC) from different sources.
METHODThe expression levels of HRM on HS/PC from umbilical cord blood (UCB), mobilized peripheral blood (mPB) and bone marrow (BM) were assessed using a highly sensitive 4-color flow cytometric analysis.
RESULTSUCB-derived CD34(bright) cells, as well as mPB- and BM-derived CD34(bright) cells strongly expressed CD44, CD11a, CD18, CD62L, CD31 and CD49d. On the other hand, significantly lower expressions of CD49e, CD49f, CXCR-4 and CD54 on UCB-derived CD34(bright) and CD34(bright)CD38(-) cells, compared with those on mPB- and BM-derived CD34(bright) and CD34(bright)CD38(-) cells, were observed. None of UCB-, mPB- and BM-derived CD34(bright) cells expressed other chemokine receptors, including CCR-1, CCR-2, CCR-3, CCR-5, CXCR-1, CXCR-2, CXCR-3 and CXCR-5. Another striking finding was that only mPB-derived CD34(bright) cells expressed significant levels of both the matrix metalloproteinases MMP-2 \[(11.4 +/- 4.9)%\] and MMP-9 \[(27.6 +/- 7.8)%\].
CONCLUSIONHS/PC from UCB have some defects of expression of HRM repertoire, which might partly explain the cause(s) of delayed hematopoietic reconstitution after UCB transplant.
Antigens, CD34 ; immunology ; Bone Marrow Cells ; cytology ; immunology ; metabolism ; CD11a Antigen ; immunology ; CD18 Antigens ; immunology ; Cell Adhesion Molecules ; metabolism ; Cells, Cultured ; Fetal Blood ; cytology ; Flow Cytometry ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cells ; cytology ; immunology ; metabolism ; Humans ; Hyaluronan Receptors ; immunology ; Infant, Newborn ; Matrix Metalloproteinases, Secreted ; metabolism ; Platelet Endothelial Cell Adhesion Molecule-1 ; immunology ; Receptors, CXCR4 ; metabolism