Expression of MMP-2, MMP-9 and MMP-11 in dermatofibroma and dermatofibrosarcoma protuberans

Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are the spindle cell mesenchymal neoplasms of the dermis and subcutis. Their histogenesis still remains uncertain and controversial. Traditionally, CD34 and factor XIIIa or other markers have been widely used to distinguish these two diseases. However, the results of these markers reveal overlapping and they lack specificity. Formalin-fixed, paraffin-embedded blocks were collected from the biopsied cases in Kaohsiung Medical University Hospital in Taiwan between 2004 and 2006. This study included 19 cases of DF and 17 cases of DFSP. Immunohistochemical analysis using antibodies CD34, matrix metalloproteinases (MMP)-2, MMP-9, and MMP-11 was performed. We found that the expression of CD34, MMP-2 and MMP-11 shows significant statistical differences in Immunohistochemistry (IHC) study positive or negative reactivity (positive of CD34 in DFSP and positive of MMP-2 and MMP-11 in DF; p = 0.03, p < 0.001, and p < 0.001, respectively) between DF and DFSP. The result for expression of MMP-9 reveals no differences. The results indicate that the pathogenesis of DF and DFSP are affected by different expressions of extracellular matrix proteins. Metalloproteinases may play a direct role in these two diseases. Since no single marker can completely distinguish DF from DFSP, a combination of more than two or three stains may elevate the accuracy of diagnosis.     

Expression levels and association of gelatinases MMP-2 and MMP-9 and collagenases MMP-1 and MMP-13 with VEGF in synovial fluid of patients with arthritis

This study was performed to provide evidence, albeit indirectly, as to which matrix metalloproteinases (MMPs), among the gelatinases MMP-2 and MMP-9 and the collagenases MMP-1 and MMP-13, play a more proactive role in the angiogenic process in arthritic joint. Joint fluid was collected from 33 patients with rhuematoid arthritis (RA) and osteoarthritis (OA), and protein (MMPs and vascular endothelial growth factor (VEGF)) levels were measured by ELISA, and the association of MMPs with VEGF was evaluated in joint fluid of patients with RA or OA. The levels of collagenases (total MMP-1 and total MMP-13) and gelatinases (total MMP-2 and total MMP-9) in RA joint fluid were significantly higher than those in OA fluid. Total MMP-9 levels were significantly associated with VEGF levels in RA fluids, but not in OA fluid, while total MMP-13 levels were strongly associated with VEGF levels in both RA and OA fluid. However, total MMP-2 and total MMP-1 levels were not associated with VEGF levels in either RA or OA joint fluid. Our results indirectly suggest that in RA and OA, MMP-9 and MMP-13 may play a more important role in angiogenesis than MMP-2 and MMP-1.     

结肠癌组织中MMP-7、MMP-9的表达及意义

目的观察结肠癌组织中基质金属蛋白酶（MMP）-7、MMP-9的表达，探讨其在结肠癌浸润、转移中的作用。方法采用免疫组化SP法检测50例结肠癌及其切缘组织中MMP-7、MMP-9的表达。结果肿瘤组织中MMP-7、MMP-9阳性表达率分别为68．00％和82．00％，标本切缘组织中分别为0和24．00％，两者相比，P均〈0．05，MMP-7、MMP-9在有淋巴结转移者中的阳性表达率为86．96％和91．30％，显著高于无淋巴结转移者的51．85％和74．07％，P均〈0．05；MMP-7、MMP-9在结肠癌组织中的表达呈正相关，r=0．84，P〈0．05。结论MMP-7、MMP-9高表达可能与结肠癌的浸润、转移有关。     

Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease

OBJECTIVES: Our hypothesis was that functional polymorphisms in matrix metalloproteinase (MMP) genes may act as susceptibility factors for the development of coronary aneurysms (CAs). BACKGROUND: Different forms of remodeling have been described at the level of coronary arteries; CA, reported in 1% to 5% of patients with angiographic evidence of coronary artery disease (CAD), are one of them. Matrix metalloproteinases have been implicated in the pathogenesis of aneurysm development through increased proteolysis of extracellular matrix proteins. METHODS: We screened 3,862 patients who underwent coronary angiography and identified 113 patients with CAD with at least one CA (CA group); these patients were matched with 226 patients with CAD without CA (control group). The -1,306 C/T MMP-2, 5A/6A MMP-3, CA-repeat MMP-9 and -82 A/G MMP-12 polymorphisms were determined. RESULTS: The MMP-2, MMP-9 and MMP-12 polymorphisms were not associated with CA. By contrast, the 5A/5A genotype of MMP-3 was significantly more frequent in the CA group than in the control group (31% vs. 18%, p = 0.015); similarly, the MMP-3 5A allele was more frequent in the CA group (p = 0.009). Three variables were independently associated with CA: the MMP-3 5A/5A genotype (odds ratio [OR] = 2.23, 95% confidence interval [CI] [1.27 to 3.93]), a previous myocardial infarction (OR = 1.91, 95% CI [1.14 to 3.20]) and a history of aortic aneurysm (OR = 21.06, 95% CI [2.35 to 188]). CONCLUSIONS: The MMP-3 5A allele is associated with the occurrence of CA. Our results suggest that an increased proteolysis in the arterial wall may act as a susceptibility factor for the development of CA in patients with coronary atherosclerosis.     

MMP-7、MMP-13在直肠癌中的表达及临床意义

目的研究直肠癌中MMP-7和MMP-13的表达情况,探讨它们与直肠癌侵袭和转移的关系及临床意义.方法对60例直肠癌、22例癌旁正常组织进行MMP-7和MMP-13免疫组化染色.结果MMP-7在癌组织中表达明显高于癌旁正常组织,二者之间差异显著(P＜0.01);MMP-13在癌旁正常组织中无表达,MMP-13在直肠癌细胞和间质细胞中均有阳性表达,但主要在间质细胞中表达.MMP-7表达与肿瘤分化程度、Dukes分期及淋巴结转移呈正相关(P＜0.05),MMP-13表达与肿瘤分化程度、Dukes分期及淋巴结转移无相关性(P＞0.05).结论直肠癌组织中MMP-7的表达与肿瘤进展有一定关系,可被视为一种反映直肠癌生物侵袭性的有价值的标志物,MMP-13可能参与了间质成分较强的降解反映过程,从而使肿瘤更易侵袭和转移.     

基质金属蛋白酶-9与肺纤维化

基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)是一种金属离子依赖的蛋白酶,通过多种途径参与特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的发病机制,本文就MMP-9的基本特性及其与肺纤维化的关系进行综述。     

Effects of PDGF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression

Background and aimsAtherosclerosis is a chronic inflammatory process involving the activity of several cytokines and growth factors. Platelet-derived growth factor-A (PDGF-A) and PDGF-B are important mitogens and chemoattractants for monocytes as well as smooth muscle cells. We sought to identify the role of PDGF-C and PDGF-D, two new members of the PDGF family, in monocyte migration and differentiation. We also assessed their effects in regulating matrix metalloproteinase-2 (MMP-2) and MMP-9, which are important for cell migration.Methods and resultsPDGF-C and PDGF-D were expressed in macrophages, smooth muscle cells, and endothelial cells in human atherosclerotic plaques, as shown by immunohistochemical analysis. PDGF-C and PDGF-D mRNA and protein expression was induced after differentiation of THP-1 monocytes to macrophages, and both PDGF-C and PDGF-D induced MMP-9 mRNA expression in a concentration-dependent manner. Treatment of cells with PDGF-C or PDGF-D enhanced the secretion of MMP-2 and MMP-9 in a cell-dependent manner. In a migration assay using a Boyden chamber with 8 μm pore size, PDGF-C and PDGF-D attracted THP-1 monocytes in a concentration-dependent manner.ConclusionsOur data suggest that PDGF-C and PDGF-D, like PDGF-A and PDGF-B, play important roles in atherosclerosis by stimulating MMP activity and influencing monocyte migration.     

血管抑素对糖尿病肾病大鼠MMP-2和MMP-9表达的影响

目的 探讨腺相关病毒介导血管抑素基因(rAAV-AS)对糖尿病肾病(DN)大鼠肾皮质中基质金属蛋白酶-2(MMP-2)和-9(MMP-9)表达的影响.方法 采用链脲佐菌素(STZ)腹腔注射法建立糖尿病动物模型.SD大鼠随机分为对照组、糖尿病组、rAAV空载体组和rAAV-AS治疗组.第10周检测大鼠的微量白蛋白尿(MAU)及肾脏肥大指数、肾功能、血糖、糖化血红蛋白;免疫组化观察肾皮质内MMP-2、MMP-9,光镜观察病理变化.结果 治疗组肾皮质中MMP-2、MMP-9的表达高于糖尿病组,但都低于对照组,免疫组化有相应的改变.结论 rAAV-AS对DN大鼠肾脏具有保护作用,其可能机制与其上调大鼠肾皮质中MMP-2、MMP-9的表达,从而减少肾组织细胞外基质(ECM)的聚集有关.     

Matrix metalloproteinase-2 (MMP-2) and MMP-9 in pulmonary pathology

The lung is affected by a variety of disease processes that can lead to considerable morbidity and mortality. As the lung is the only organ for respiration and gas exchange, the structural and functional integrity of the lung is of primary importance. Various pathological processes affect the extracellular matrix (ECM) of the lung in an adverse manner, causing destruction of tissue integrity followed by tissue remodeling, which together impair normal pulmonary function. Matrix metalloproteinases (MMPs) are neutral proteinases that are involved in the breakdown and remodeling of the ECM under a variety of physiological and pathological conditions. MMP-2 and MMP-9, collectively known as the gelatinases, are particularly important in the pathogenesis of inflammatory, infectious, and neoplastic diseases in many organs including the lung. This review examines the expression of MMP-2 and MMP-9 in disease of the lung and discusses the role these gelatinases may play in disease progression.     

Twist1,MMP-2和MMP-9在结直肠癌组织中的表达及意义

目的:研究Twist1、MMP-2和MMP-9蛋白在结直肠癌组织中的表达及其相互关系.方法:建立组织微阵列平台,应用免疫组织化学方法检测92例结直肠癌组织Twist1、MMP-2和MMP-9蛋白的表达情况.结果:结直肠癌中Twist1的表达率为64.1%,MMP-2和MMP-9阳性率分别为66.3%和67.4%;Twi...     

eNOS gene transfer inhibits smooth muscle cell migration and MMP-2 and MMP-9 activity

Vascular smooth muscle cell (SMC) migration is a critical step in the development of neointima after angioplasty. Matrix metalloproteinases (MMPs) degrade the basement membrane and the extracellular matrix, facilitating SMC migration. Transfer of the endothelial nitric oxide synthase (eNOS) gene to the injury site inhibits neointima formation. Neither the signaling pathways leading to NO-mediated inhibition of SMC migration and proliferation nor the alterations in these pathways have been characterized. We hypothesize that NO inhibits SMC migration in part by regulating MMP activity. To test this hypothesis, we transfected cultured rat aortic SMCs with replication-deficient adenovirus containing bovine eNOS gene and analyzed the conditioned medium for MMP activity. We observed that eNOS gene transfer significantly (P<0.05) inhibited SMC migration and significantly (P<0.05) decreased MMP-2 and MMP-9 activities in the conditioned medium. Similarly, addition of the NO donor DETA NONOate and 8-bromo-cGMP to the culture medium significantly decreased MMP-2 and MMP-9 activities in the conditioned medium collected 24 hours after treatment. Furthermore, Western blot analysis of the conditioned medium collected from eNOS gene-transfected SMCs showed a significant increase in tissue inhibitor of metalloproteinases-2 (TIMP-2) levels. Our data suggest that NO decreases MMP-2 and MMP-9 activities and increases TIMP-2 secretion, and this shifts the balance of MMP activity, which may favor the inhibition of cell migration because of inhibition of extracellular matrix degradation.     

Differential Expression of Three Matrix Metalloproteinases, MMP-19, MMP-26, and MMP-28, in Normal and Inflamed Intestine and Colon Cancer

Several matrix metalloproteinases (MMPs) have been implicated in intestinal inflammation, mucosal wound healing, and cancer progression. The purpose of this study was to examine the cellular location and putative function of MMP-19, MMP-26 (matrilysin-2), and MMP-28 (epilysin), in normal, inflammatory, and malignant conditions of the intestine. Peroperative tissue specimens from patients with ulcerative colitis (UC) (n = 16) and archival tissue samples of ischemic colitis (n = 9), Crohn's disease (n = 7), UC (n = 8), colon cancer (n = 20), and healthy intestine (n = 5) were examined using immunohistochemical analyses with polyclonal antibodies. Unlike many classical MMPs, MMP-19, MMP-26, and MMP-28 were all expressed in normal intestine. In inflammatory bowel disease (IBD), MMP- 19 was expressed in nonmigrating enterocytes and shedding epithelium. MMP-26 was detected in migrating enterocytes, unlike MMP-28. In colon carcinomas, MMP-19 and MMP-28 expression was downregulated in tumor epithelium. Staining for MMP-26 revealed a meshwork-like pattern between cancer islets, which was absent from most dedifferentiated areas. Our results suggest that MMP-19 is involved in epithelial proliferation and MMP-26 in enterocyte migration, while MMP-28 expression is not associated with inflammatory and destructive changes seen in IBD. In contrast to many previously characterized MMPs, MMP-19 and MMP-28 are downregulated during malignant transformation of the colon and may play a prominent role in tissue homeostasis.     

Association of MMP-2 and MMP-9 expression with recurrences in primary spontaneous pneumothorax

Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is still a troublesome complication for most patients. This study intended to determine the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in type II pneumocytes of patients with PSP and its relation with recurrence. Ninety-one patients who had undergone needlescopic video-assisted thoracoscopic surgery wedge resection of lung with identifiable blebs for PSP were included in this study. Immunohistochemical (IHC) staining was used to measure the expression of MMP-2 and MMP-9 in lung tissues of PSP patients. The results were further correlated with clinicopathological parameters and recurrence rates using chi-square or Fisher's exact test. The value of MMP-2 and MMP-9 for overall recurrence was analyzed by univariate and multivariable Cox regression model. IHC data revealed that MMP-2 and MMP-9 staining was predominantly observed in type II pneumocytes of patients with PSP. We found that MMP-2 and MMP-9 expression in PSP, especially male PSP patients, was significantly correlated with recurrence. In the univariate and multivariate analyses, MMP-2 and MMP-9 were statistically significant risk factors for overall recurrence in PSP patients. Therefore, high expression levels of MMP-2 and MMP-9 in type II pneumocytes show a positive correlation with PSP recurrence risk. Further studies are needed to validate whether reduction of MMP-2 and MMP-9 expression may be a promising way for decreasing the risk of PSP recurrence in the future.     

微粒皮种植对糖尿病溃疡创面中MMP-2 MMP-9水平的影响

目的探讨微粒皮种植在治疗糖尿病溃疡过程中,溃疡肉芽组织基质金属蛋白酶(MMP)-2、MMP-9的动态变化。方法对18例糖尿病溃疡患者进行微粒皮种植治疗,在治疗前和治疗后7 d、14 d分别采集创面肉芽组织。用酶联免疫法检测肉芽组织中MMP-2、MMP-9浓度,同时观察溃疡愈合情况。结果微粒皮种植治疗后7 d、14 d的溃疡面积在各观察时间点均较治疗前缩小(P0.05);该组肉芽组织MMP-2浓度逐渐下降,在治疗后第14天时降至最低(P0.05); MMP-9从治疗后逐渐降低,但各时点与治疗前相比,差异均无统计学意义;肉芽组织中MMP-2的浓度与溃疡面积大小呈正相关关系(r=0.385,P0.05)。结论微粒皮种植治疗可降低糖尿病溃疡肉芽组织中MMP的浓度,MMP-2的浓度可能是影响糖尿病皮肤溃疡愈合的相关因素。     

MMP-2、MMP-9和VEGF在肾癌中的表达与临床意义

目的 探讨基质金属蛋白酶-2、-9(MMP-2、MMP-9)与血管内皮生长因子(VEGF)在肾癌组织中的表达与临床分期的意义.方法 蛋白免疫印迹法、ELISA和逆转录聚合酶链反应法(RT-PCR)检测癌组织MMP-2、MMP-9,蛋白质免疫印迹法和RT-PCR检测癌组织VEGF.结果 肾癌组织中MMP-2、MMP-9和VEGF明显表达,随着病程的进展MMP-2、MMP-9和VEGF活性逐渐增高,以Ⅳ期晚期最明显,VEGF与MMP-2、MMP-9表达具有正相关性.结论 MMP-2、MMP-9和VEGF参与了肾癌临床病情进展和发病机制.     

Enhanced production of MMP-1, MMP-3, MMP-13, and RANTES by interaction of chondrocytes with autologous T cells

It has been reported that T cells and chondrocytes interact through cell surface molecules such as MHC, CD4 or CD8 in osteoarthritis (OA) and T cells are activated. The objective of this study is to investigate the responses of chondrocyte–T cell interaction in terms of metalloprotease (MMP) and chemokine production. Articular cartilage and autologous blood were obtained from patients with OA and fracture who under went prosthetic surgery. Synovial fluid (SF) was collected from OA patients. Isolated chondrocytes were co-cultured with autologous T cells. SF cells were analyzed by immunostaining or Alcian blue staining. The production of MMP-1, MMP-3, MMP-13, and regulated on activation, normal T expressed and secreted (RANTES) was enhanced by direct co-culture compared to indirect co-culture using Transwell. Production ratio of RANTES in OA was significantly higher than non-arthritic samples. CD3 positive mononuclear cells and chondrocyte-like cells were found in SF. Chondrocyte–T cell contact was more adhesive in OA samples. These results showed the production of MMPs and RANTES was enhanced by the interaction and that chondrocyte–T cell contact was possible in vivo.