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.     

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.     

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.     

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.     

Evaluation of MMP-1, MMP-8, MMP-9 serum levels in patients with adrenal tumors prior to and after surgery

The aim of the study is to evaluate MMP-1, MMP-8 and MMP-9 serum levels in patients with adrenal tumors prior to and after surgery. Metalloproteinase-1 (MMP-1), MMP-8 and MMP-9 serum levels were evaluated in 43 patients operated on at our clinic between 1997-1999. Forty-one (95.3%) patients underwent adrenalectomy. Two (4.7%) patients were disqualified from surgery due to infiltration of adjacent tissues. MMP-1, MMP-8 and MMP-9 serum levels were determined at the admission and in case of surgery again one month after the operation. ELISA assay (K&D) was applied. Tumor type was determined on the basis of clinical, hormonal and histopathological examination. The correlation between MMP levels and tumor sizes was also evaluated. Patients were divided into 6 groups. Group I included 11 patients with adrenocortical carcinoma (4 with Cushing's syndrome and 7 with incidentalomas); group II--6 patients with benign hormonally active adrenocortical adenoma (4 with Cushing's syndrome and 2 with Conn's syndrome); group III--patients with benign, hormonally inactive adenocortical adenoma; group IV--6 patients with benign, hormonally active phaeochromocytoma; group V--4 patients with hormonally inactive phaeochromocytoma; group VI--5 patients with hormonally inactive adrenal tumors of extraglandular origin (2 myolipomas, 2 fibrolipomas, 1 hammartoma). The control group comprised 10 healthy individuals. Increased MMP-8 and MMP-9 levels were noted in patients with benign and malignant adrenal tumors. No increase of MMP levels was found in patients with tumors of extraglandular origin. The increased MMP-8 and MMP-9 levels occurred most frequently in patients with adrenocortical and hormonally active adrenomedullar cancer, and most rarely in patients with hormonally active adrenocortical tumors. MMP-8 and MMP-9 serum levels did not significantly differ between patients with adrenocortical incidentaloma cancers and in patients with benign incidentalomas. MMP-8 and MMP-9 levels were not increased in patients with inoperable adrenocortical cancers. Serum MMP-1 levels were not increased in patients with benign and malignant adrenal tumors. After surgery, MMP-8 and MMP-9 levels decreased significantly in patients with adrenocortical cancers, whereas the decrease of these MMPs in patients with benign tumors, although noticeable, was not statistically significant. MMP-8 and MMP-9 levels decreased significantly in all patients with increased preoperative levels, although they remained higher than the maximum normal values only in few patients (in 7 and 2 patients, respectively). No correlation between the levels of evaluated MMPs and tumor sizes were found.     

结肠癌组织中p15、MMP-2、MMP-9的表达及意义

目的 探讨p15、基质金属蛋白酶(MMP)-2、MMP-9在结肠癌中的表达及意义.方法 采用免疫组化SP法检测50例结肠癌组织、癌旁组织和正常切缘组织中的p15、MMP-2、MMP-9.结果 结肠癌组织、癌旁3 cm和正常切缘中,p15的阳性表达率分别为84%、94%、100%,MMP-2分别为76%、20%、0,MMP-9分别为82%、44%、0,三种组织中三项指标相比,P均<0.05.癌组织中三项指标的表达与肿瘤的分化程度、Dukes分期及有无淋巴结转移密切相关. 结论 p15的低表达和MMP-2、MMP-9的过表达在结肠癌的发生、发展及其浸润和转移中具有重要作用.     

急性冠状动脉综合征患者MMP-9、MMP-2的临床意义

目的观察不同冠心病患者的血清的基质金属蛋白酶(MMPs)及其演变,探讨MMPs与急性冠状动脉综合征的关系。方法用酶联免疫吸附法(ELISA)检测了32例急性心肌梗死(AMI),30例不稳定型心绞痛,20例稳定型心绞痛和16例健康对照者血清MMP-9,MMP-2和组织型基质金属蛋白酶抑制物-2(TIMP-2)水平,并比较上述指标与不同类型冠心病的关系及其演变。结果AMI患者血清MMP-9水平高于不稳定型心绞痛组、稳定型心绞痛组和对照组,分别为(191.91±150.10)ng/ml,(110.84±96.29)ng/ml,(69.30±55.85)ng/ml和(80.13±34.94)ng/ml。MMP-2、TIMP-2四组间比较差异无显著性。MMP-9在AMI患者中发病早期升高后持续到3~5d。MMPs与心肌损伤标志物无相关关系。结论血清MMP-9是预示斑块破裂中的主要MMPs之一,但它不能预测心肌坏死的程度。     

库肯勃瘤组织VEGF,TGF-β1,MMP-2,MMP-9表达的意义

目的:研究VEGF,TGF-β1,MMP-2,MMP-9在卵巢原发上皮性肿瘤、库肯勃瘤中的表达及其相关性,以探讨其在库肯勃瘤发生、发展中的作用.方法:应用免疫组化S-P法检测VEGF,TGF-β1,MMP-2,MMP-9在45例卵巢原发上皮性肿瘤、38例库肯勃瘤中的表达情况.结果:VEGF、TGF-β1在卵巢原发上皮性肿瘤和库肯勃瘤组织中的表达显著高于正常卵巢组织(VEGF:x2=5.318,P=0.021;x2=22.985,P=0.001.TGFβ1:x2=9.778,P=0.002;x2=12.584,P=0.001).MMP-2,MMP-9在正常卵巢组织中表达缺如;VEGF,MMP-2,MMP-9在库肯勃中阳性表达率明显高于卵巢原发上皮性肿瘤(VEGF:x2=13.149,P=0.001;MMP-2:x2=33.668,P=0.001;MMP-9:x2=38.839,P=0.001);TGF-β1阳性表达率在卵巢原发上皮性肿瘤和库肯勃瘤之间无显著差异.VEGF,TGF-β1,MMP-2,MMP-9在卵巢原发上皮性肿瘤、库肯勃瘤中,任意两指标阳性表达均有正相关性(P＜0.05或P＜0.01).结论:VEGF,TGF-β1,MMP-2,MMP-9参与卵巢癌、库肯勃瘤的发生、发展及演进过程,并可为卵巢上皮性肿瘤及库肯勃瘤的鉴别诊断提供一定依据.     

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...     

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.     

实验性肝纤维化逆转过程中基质金属蛋白酶表达的动态研究

探讨基质金属蛋白酶在实验性肝纤维化逆转过程中的表达及意义。建立大鼠实验性四氯化碳中毒性肝纤维化模型,采用核酸原位杂交和免疫组化法检测实验性肝纤维化自然逆转过程中MMP-13、MMP-2、MT—MMP2的来源细胞、时序和量的变化。MMP-13、MMP-2、MT—MMP2在间质细胞和部分肝细胞表达,MMP-13先维持在一定水平,然后逐渐减弱;MMP-2、MT—MMP2先增强后减弱。肝脏间质细胞是基质金属蛋白酶的主要来源细胞,MMP-13、MMP-2、MT—MMP2表达与肝纤维化程度相关,在肝纤维化逆转过程中起重要作用。     

MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in patients with rheumatoid arthritis and psoriatic arthritis

OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PA) are both chronic rheumatic inflammatory diseases characterized by disruption of the extra-cellular matrix (ECM) protein of the cartilage, likely induced by proteolytic enzymes such as matrix metalloproteases (MMPs). The goal of this study was to quantify the expression of MMPs such as MMP-2 and MMP-9, and their physiological tissue inhibitors TIMP-2 and TIMP-1, respectively, in serum and synovial fluid. METHODS: Serum and synovial fluid from 24 RA patients and 17 PA patients were studied to determine the levels of MMP-2 and MMP-9 proteolytic activity using a modified gelatin zymography procedure. TIMP-1 and TIMP-2 were measured by a commercially available ELISA kit. RESULTS: Our results show that MMP-2 was detected in the latent form only, while MMP-9 was present in latent and active form. Both gelatinases were more concentrated in synovial fluid than in serum, and TIMP-1 and TIMP-2 concentrations were also more elevated in synovial fluid than in serum. CONCLUSIONS: To investigate the remodelling of cartilage ECM proteins, the evaluation of synovial fluid concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 is more reliable than that determined in serum. In view of these data, MMPs inhibitors might represent a possible target for new therapies delivered directly in the joint space.     

TIMP-1、MMP-2、MMP-9在大肠癌组织中表达的临床意义

目的 研究TIMP-1、MMP-2和MMP-9在大肠癌组织中表达的临床意义.方法 采用免疫组化SP法检测50例大肠癌、10例正常大肠黏膜组织中TIMP-1、MMP-2和MMP-9的表达.结果 TIMP-1、MMP-2、MMP-9在正常组织中的表达均较低,而它们在大肠癌组织中阳性率均较高(P<0.05).结论 TIMP-1、MMP-2、MMP-9与大肠癌临床病理参数有关系.TIMP-1、MMP-2和MMP-9可能是大肠癌侵袭转移的分子标记物.     

早期应用辛伐他汀对急性冠状动脉综合征血清基质金属蛋白酶及其抑制因子和高敏C-反应蛋白水平的影响

目的:研究早期应用辛伐他汀对急性冠状动脉综合征患者稳定斑块、减少炎症反应的作用.方法:采用随机、对照方法,将137例急性冠状动脉综合征患者分为他汀治疗组(辛伐他汀20 mg/d,n=69)和他汀对照组(n=68);于发病12～48小时和治疗8周后分别测定血清基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制因子-1(TIMP-1)、MMP-9/TIMP-1、高敏C-反应蛋白(hs-CRP)水平.另设健康对照组(n=60)与之对照.结果:①治疗前他汀治疗组和他汀对照组的血清MMP-1、MMP-9、MMP-9/TIMP-1、TIMP-1、hs-CRP水平均较健康对照组明显增高(P＜0.01～0.001),与血脂水平不相关.②他汀治疗组经辛伐他汀治疗8周后血清MMP-1、MMP-9、MMP-9/TIMP-1、hs-CRP水平较治疗前均明显降低(P＜0.001),他汀对照组除血清hs-CRP水平降低外(P＜0.05),其他各项指标均无变化.结论:早期应用他汀治疗,可减少急性冠状动脉综合征患者的冠状动脉粥样斑块基质成分的降解和炎症反应,具有稳定斑块作用.     

MMP-8, MMP-9 and Neutrophil Elastase in Peripheral Blood and Exhaled Breath Condensate in COPD

Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airflow limitation associated with chronic inflammation involving cytokines and metalloproteinases (MMPs). MMP-8, MMP-9 and neutrophil elastase (NE) are known to be implicated in COPD but the factors influencing activation and suppression remain unclear. This study aimed to compare MMP-8, MMP-9 and NE in the peripheral blood of COPD patients and controls and to likewise assess exhaled breath condensate (EBC) for these MMPs. Peripheral blood micro(mi)RNA139-5p levels, which may regulate MMPs in COPD, were also measured. Blood and EBC were collected from COPD patients (stable and during exacerbations) and healthy controls. Expression of mRNA for MMP-8, MMP-9, NE and miRNA-139-5p expression in peripheral blood mononuclear cells (PBMCs) was measured using qRT-PCR. MMP-8, MMP-9 and NE protein in plasma as well as MMP-8 and MMP-9 protein in EBC were analysed by enzyme-linked immunoassays. PBMCs from COPD patients showed greater expression of mRNA for MMP-8 (p = 0.0004), MMP-9 (p = 0.0023) and NE (p = 0.0019). PBMC expression of mRNA for NE was significantly higher in COPD exacerbations compared to stable cases (p < 0.05). Expression of mRNA for MMP-9 and NE correlated negatively with spirometry in patients (p < 0.05). Plasma from COPD patients showed greater levels of protein for MMP-8 (p = 0.003), MMP-9 (p = 0.046) and NE (p = 0.018). MMP-8 protein levels were lower in the EBC of COPD patients (p < 0.0001). In PBMCs, enhanced expression of mRNA for MMP-9 and NE is associated with COPD and may correlate with disease severity and exacerbations.