The relationship between matrix metalloproteinases-9 and CD15s antigen in angiogenesis of gastric carcinoma

Objective： To investigate the relationship between matrix metalloproteinases-9 （MMP-9） and sialyl Lewis X （CD15s） antigen in invasion and metastasis of gastric carcinoma. Methods： Expression of CD105, MMP-9 and CD15s in 47 cases of gastric carcinoma undergone radical surgery were evaluated by SP immunohistochemical staining using the respective monoclonal antibody. The microvessel density （MVD） marked with CD105 was detected. Correlation between MVD and MMP-9, CD15s was also statistically analyzed. Results： The MVD in both MMP-9 and CD15s positive expression group was higher significantly than that in MMP-9 or CD15s positive expression alone group, and it was also significantly higher than that in both MMP-9 and CD15s negative expression group. Conclusion： MMP-9 is a marker of invasion and CD15s is a marker of metastasis in gastric carcinoma. Combining detection of MMP-9 and CD15s has certain clinical significance for diagnosis, treatment and assessing the prognosis for gastric caner.

脑泰方提取物干预大鼠脑缺血后MMP-9-mRNA及PA-mRNA表达研究

目的研究大鼠脑缺血后益气活血中药脑泰方提取物(黄芪、川芎、地龙、僵蚕)干预对缺血区脑水肿及MMP-9-mRNA、PA-mRNA表达的影响。方法随机将SD大鼠分为假手术组、模型组、脑泰方提取物(NTE)低、中、高剂量组(3,9,27g/kg)。各组大鼠预处理ig给药连续3d,每日1次,MCAO模型制备术后ig给药1d。术后1d取材检测各组脑组织含水量,RT-PCR检测MMP-9-mRNA及PA-mRNA表达。结果实验表明高、中NTE组与模型组比较,脑含水量均有明显降低(P<0.05)。NTE高剂量组脑缺血区MMP-9-mRNA、PA-mRNA表达明显降低(P<0.05)。结论脑泰方提取物干预可减轻脑水肿的发生,可能是通过降低MMP-9-mRNA及PA-mRNA的表达,减少MMP-9、PA的生成,发挥保护急性脑缺血血脑屏障的作用。

吡格列酮对高脂血症大鼠主动脉组织MMP-2、MMP-9表达的影响

目的观察吡格列酮对高脂血症大鼠主动脉基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)表达的影响。方法 26只雄性SD大鼠随机分成普通饲料组(n=9)和高脂饲料组(n=17),分笼饲养,12周后检测空腹血脂水平,以确定高脂饲料组高脂血症大鼠造模是否成功;再将成模大鼠随机分成模型组(n=8)和吡格列酮组(n=9)。第13周起予吡格列酮组大鼠予吡格列酮混悬液连续灌胃4周,余2组用相应量的蒸馏水灌胃4周,平行检测2组大鼠血脂水平,免疫组化检测主动脉MMP-2、MMP-9表达,并用Image-Pro Plus 6.0图像分析系统分析染色结果。结果高脂饲料喂养12周大鼠总胆固醇(TC)、三酰甘油(TG)和低密度脂蛋白胆固醇(LDL-C)水平较对照组明显升高(P<0.05),表明造模成功。吡格列酮组主动脉MMP-2、MMP-9表达水平较之模型组明显降低(P<0.05)。结论吡格列酮能通过抑制主动脉MMP-2、MMP-9表达,有利于斑块的稳定性增加。

Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.

Clinicopathological and prognostic role of MMP-9 in esophageal squamous cell carcinoma: a meta-analysis

Objective： Many studies reported that matrix metalloproteinase-9 （MMP-9） participated in the development of esophageal squamous cell carcinoma （ESCC） and resulted in poor prognosis, however, they all included few patients and had inconsistent results. So we conducted a meta-analysis to explore the correlation between overexpression of MMP-9 and the clinicopathological characteristics and overall survival （OS） of ESCC. Methods： PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, Google Scholar and other databases were searched for relevant studies. The Newcastle-Ottawa quality assessment scale was used to assess the methodological quality of included study and RevMan 5.2 software was used to conduct meta-analysis. Results： A total of 35 studies were included, and the results of meta-analysis showed that overexpression of MMP-9 was associated with grade of differentiation [well/moderate vs. poor： odds ratio （OR）： 0.39, 95% confidence interval （CI）： 0.29-0.52; P〈0.00001], lymph node metastasis （negative vs. positive： OR： 0.24, 95% CI： 0.16-0.34; P〈0.00001）, TNM stage （T1/T2 vs. T3/T4： OR： 0.28, 95% CI： 0.14-0.54; P=0.0002）, the depth of invasion （T1/T2 vs. T3/T4： OR： 0.29, 95% CI： 0.17-0.49; P〈0.00001）, and vascular invasion of ESCC （negative vs. positive： OR： 0.35, 95% CI： 0.21-0.58; P〈0.0001）, and also associated with poor overall survival ofESCC （HR： 2.17, 95% CI： 1.32-3.57; P=0.002）. Subgroup analysis showed that more than 10% of carcinoma cell staining was associated with significant increase of mortality risk （HR： 2.44, 95 % CI： 1.16-5.15; P=0.02）, and sensitive analysis suggested that MMP-9 was an independent prognostic factor in ESCC （HR： 1.49, 95% CI： 1.16-1.91; P=0.002）. Conclusions：On the basis of limited evidence, overexpression of MMP-9 may be a potential independent prognosis factor of ESCC patients in Asia, and high-quality studies assessing the prognostic significance of MMP-9 for ESCC patients are still needed.

Multifactor Regulation on Expressions of MMP-9 and TIMP-1 in Endometrial Stromal Cells

Objective To investigate the regulatory effect of multifactor on the matrix metalloproteinases-9 （MMP-9） and the tissue inhibitor of metalloproteinase-1 （TIMP-1） in endometrial stromal cells. Methods The endometrial stromal cells separated from the proliferative endometrial tissues were incubated with medium alone, 17-β estradiol （E2,10^-8 mol/L）, medroxyprogesterone acetate （MPA, 10^-6 mol/L）, E2（10^-8 mol/L）＋MPA （10^-6 mol/L）, E2 （10^-8 mol/L）＋MPA （10^-6 mol/L）＋RU486 （10^-5 mol/L） or HB-EGF （10 ng/ml） for 48 h respectively. The expressions of MMP-9 and TIMP-1 were detected by in situ hybridization, immunocytochemistry, reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blotting. Results Compared with control group [mRNA, 0. 729 ± 0. 090 （MMP-9） and 1.056± 0.154 （TIMP-1）; protein, 0.545 ±0.086 （MMP-9） and 0.745 ±0.154 （TIMP-1）], expressions of MMP-9 and TIMP-1 in E2 alone, progestin alone or E2 combined with progestin group were respectively：mRNA, 0.413 ± 0.069, 0.402 ± 0.073 and 0.407 ± 0.039; 0.487 ± 0.093, 0.503 ± 0.093 and 0.468 ± 0.075：protein, 0.294 ± 0.076, 0.331 ±0.064 and 0.265 ±0.049; 0.425 ±0.085, 0.397 ±0.065 and 0.435 ± 0.099. RU486 weakened the expression level of down-regulation, while HB-EGF elevated the level of MMP-9 and TIMP-1 after 48 h treatment （mRNA, 0.955 ± 0.068 and 1.396 ± 0.238; protein, 0. 780 ± 0.109 and 0.985 ± 0.165）. Conclusions 1） Both E2 and progestin can down-regulate the expressions of MMP-9 and TIMP-1 in endometrial stromal cells, but RU486 can inhibit the effect. 2） HB-EGF can elevate the level of MMP-9 and TIMP-1. 3） E2, progestin and HB-EGF have effect on the ratio of MM-P/TIMP-1.

Expressions of cyclooxygenase-2 and matrix metalloproteinase-9 in cervical carcinoma and their clinical significance

Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detect the expres- sions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE). The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results: The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% (64/72) in group ICC and 12.5% (2/16) in group NCE, P = 0.000; MMP-9: 94.4% (68/72) in group ICC and 43.8% (7/16) in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis (r = 0.296, P = 0.012) and stromal invasion (r = 0.257, P = 0.029). The expression of MMP-9 was positively correlated with FIGO stage (r = 0.329, P = 0.005) and histological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). Conclusion: The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.

Contrary Regulation of TIMP-1 and MMP-9 by Hepatocyte Growth Factor Antibody after Lung Injury

Objective To study the influence of hepatocyte growth factor (HGF) antibody on the lung expression level of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Methods Thirty male Wistar rats were randomly divided into 3 groups: control group, model group, and intervention group. Endotoxin was intratracheally infused in the model and intervention groups. HGF antibody was injected in the rats of the intervention group from day 1 to day 14, while the same volume of saline was injected in the control group. The rats were sacrificed on day 28 after endotoxin treatment. The amounts of MMP-9 mRNA and TIMP-1 mRNA were measured by reverse transcription-polymerase chain reaction, and protein expression levels of MMP-9 and TIMP-1 were measured by immunohistochemistry. Results In the model group, both mRNA and protein expression levels of TIMP-1 were significantly increased, the same as MMP-9. In the intervention group, the increase of TIMP-1 was remarkably reduced compared with the model group, while the mRNA and protein expression levels of MMP-9 were still increased. Conclusion HGF activity may accelerate the repair of lung injury through contrary regulating the expression levels of TIMP-1 and MMP-9.

乳腺癌患者血清中MMP-2、MMP-9的表达及与乳腺钼靶X线征象的关系

目的探讨乳腺癌患者血清中基质金属蛋白酶(MMP)-2和MMP-9的表达及与乳腺钼靶X线征象的关系。方法采用双抗体夹心ELISA法检测85例乳腺癌患者MMP-2、MMP-9的表达,并对所有患者进行乳腺钼靶X线扫描,然后分析两者表达与乳腺钼靶X线主要征象的关系。结果乳腺癌患者血清中MMP-2、MMP-9的表达水平分别为(113.41±10.22)μg/L、(174.27±10.97)μg/L。乳腺癌患者血清中MMP-2、MMP-9的表达水平与毛刺征、钙化征、淋巴结转移征关系密切(P<0.05)。结论 MMP-2、MMP-9的高表达是乳腺癌预后较差的预后因子,且两者均与毛刺征、钙化征、淋巴结转移征阳性关系密切,可能是其阳性征象的组织病理学基础。

Association between the-1562 C/T polymorphism in the MMP-9 promoter and phenotype of esophageal squamous cell carcinoma in northern Chinese population

Objective To conduct a case-control study on the association of the nucleotide polymorphisms in the promoter region of the matrix metalloproteinase-9(MMP-9)gene with phenotype of esophageal cancer.Methods All subjects were unrelated residents in northern regions of China.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)analysis was used to determine the MMP-9 genotypes.Results The overall distribution of genotypes in the patients was not different from that in the controls(OR=0.77,95% CI=0.45-1.34;P=0.36).There were no significant differences between the patients and the control subjects in terms of the distributions of sex and age,smoking status,alcohol dependence,pickled diet status,or history of environmental exposure.The patients were further examined with stratifications by age,sex,grade,depth of tumor invasion,lymphatic invasion,venous invasion and TNM staging.The results showed no pronounced association among the stratifications.Conclusion There is no significant association between the MMP-9 single nucleotide polymorphism genotypes and phenotype of esophageal cancer.

Association of Matrix Metalloproteinase-9 and p53 Gene Polymorphisms with Genetic Susceptibility to No-small-cell Lung Cancer

Matrix metalloproteinase-9（MMP-9） and p53 genes play an essential role in the multi-step process of tumorigenesis in lung cancer. Single nucleotide polymorphisms（SNPs） of MMP-9 and p53 genes are associated with the risk and progression of many cancers. In this study, we evaluated the association of the R279Q polymorphism of MMP-9 or the A1/A2 polymorphism of p53 gcne with the risk of no-small-cell lung cancer（NSCLC） in Han population of Northeast China. We examined the frequency of SNPs in the two kinds of genes of 50 patients with NSCLC and 50 cancer-free controls frequency-matched by age and sex. Polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） technique was used to determine the genotypes. The results indicate that the 279RR genotype in MMP-9 gene and the A1/A2 genotype in p53 gene show a significantly increased risk of NSCLC. Therefore, the MMP-9 279RR and p53 A1/A2 genotypes may be used as markers for susceptibility to NSCLC in Han population of Northeast China.

The expressions of CD147 and MMP-9 in non-Hodgkin's lymphoma cells and the relation to prognosis

Objective： The aim of this study was to investigate the expression of CD147 and matrix metalioprpteinsae 9 （MMP-9） in children with non-Hodgkin＇s lymphoma （NHL） and the relations between expressions of CD147 ＆ MMP-9 and the clinical indexes. Methods： Specimens excised from NHL patients were prepared. Expression of CD147 and MMP-9 were tested by SABC immunohistochemistry and its correlation to clinical results were analyzed in this report. Results： The positive rate of CD147 expression was 73% （45/62）, and that of MMP-9 expression was 81% （50/62）. There was a positive correlation between CD147 and MMP-9 expressions. CD147 expression intensity was linked to clinical myelo-infiltration, tumor size, LDH value, and clinical staging （P 〈 0.05）, rather than children age, gender, or immune typing （P 〉 0.05）; MMP-9 expression intensity was linked to myelo-infiltration, and clinical staging （P 〈 0.05）, rather than age, gender, immune typing, tumor size, or LDH value （P 〉 0.05）. Five-year survival rates were 78% （22/28） and 45% （15/34） in CD147 （-）-（＋） and （＋＋）-（＋＋＋） cases respectively, and those were 84% （21/25） and 43% （16/37） in MMP-9 （-）-（＋） and （＋＋）-（＋＋＋） cases respectively, the difference was significant. Conclusion： The elevated expression of CD147 and/or MMP-9 correlates with a poor clinical outcome in patients with NHL.

MMP9基因rs2274755多态性与云南汉族人群冠心病的相关性研究

目的研究基质金属蛋白酶9(MMP9)基因多态性与中国云南汉族人群冠心病(CHD)的相关性。方法采用Sequenom Mass ARRAY~对云南省第二人民医院2012年9月至2015年9月收集的198例正常人(对照组)和514例冠心病患者(冠心病组)MMP9基因rs2274755单核苷多肽(SNP)位点的多态性进行基因分型,分析该基因多态性与冠心病的相关性。结果正常对照组和冠心病组rs2274755位点基因型频率分别为GG 0.67/0.76,GT 0.31/0.22,TT 0.02/0.02,差异有统计学意义(P<0.05),两组等位基因频率分别为G 0.82/0.87,T 0.18/0.13,差异有统计学意义(P<0.05)。校正年龄、性别、体质量指数等logistic回归分析显示,rs2274755位点携带T等位基因者患冠心病风险降低[加性模型(T vs G):OR=0.72,95%CI(0.52~0.99),P=0.046;显性模型(TT/GT vs GG):OR=0.96,95%CI(0.93~1.00),P=0.028]。结论 MMP9基因多态性与云南汉族人群冠心病发生风险相关。

Matrix Metalloproteinase-9 in the Etiopathogenesis of Placenta Accreta Spectrum:A Literature Review

The recent increase in placenta accreta spectrum has been correlated with a rise in the rate of cesarean sections.A recent study provides evidence that hampered wound healing results in cesarean scar defects that lead to a failure in the normal process of decidualization and deeper adherence of trophoblasts.Matrix metalloproteinase(MMP)is crucial in every step of wound healing as it alters the wound matrix,facilitating cell migration,as well as tissue remodeling.MMP-9 expression is higher in placental and decidual tissue in cases of placenta accreta.Based on these findings,assessment of MMP-9 expression can shed new light on the etiopathology of placenta accreta spectrum disorder and can be a potential diagnostic marker.

基质金属蛋白酶-9与肾脏疾病关系的研究进展

基础研究表明，非肿瘤性肾脏疾病的病理改变实质均是细胞外基质（extra cellular matrix，ECM）在肾小球和肾间质中异常堆积的结果。ECM沉积发生机制复杂，其中基质金属蛋白酶（matrix metallo proteinases，MMPs）及其组织抑制因子（tissue inhibitors ofmetalloproteinases，TIMPs）的功能紊乱在ECM转换过程中起关健作用。MMP-9是基质金属蛋白酶家族中的重要成员之一，因其作用底物广泛，表达细胞众多，在国内外研究中备受重视。现将其与肾脏疾病关系的研究进展综述如下。

Ds-echinoside A,a new triterpene glycoside derived from sea cucumber,exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions

Ds-echinoside A (DSEA),a non-sulfated triterpene glycoside,was isolated from the sea cucumber Pearsonothuria graeffei.In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion,migration,invasion,and angiogenesis.In this study,we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2,with a half-maximal inhibitory concentration (IC50) of 2.65 μmol/L,and suppressed Hep G2 cell adhesion,migration,and invasion in a dose-dependent manner.DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo.Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9),which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis.DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1),an important regulator of MMP-9 activation.From the results of Western blotting,the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA.These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.

Effects of Danggui Buxue Decoction (当归补血汤) on Lipid Peroxidation and MMP-2/9 Activities of Fibrotic Liver in Rats

Objective:To explore the mechanism of Danggui Buxue Decoction(当归补血汤,DBD) on the liver fibrosis related to hepatic lipid peroxidation and matrix metalloproteinases(MMP) -2/9 activities.Methods: The liver fibrosis in 28 rats was induced by an injection of carbon tetrachloride(CCl_4) and fed with high lipid and low protein diet for 6 weeks,the model rats were randomly divided into the model group and DBD treated group,14 in each group,and another 10 rats as the normal group were observed as well.Rats in the DB...