MMP-12与肺部疾病的关系

基质金属蛋白酶-12(MMP-12)是基质金属蛋白酶家族中的一员,是细胞外基质降解的主要介质,结构包括前肽域、催化域和血红素结合蛋白样域.MMP-12的作用主要是基因转录和抑制物的调节两个方面.MMP-12的过度表达导致病理的细胞外基质蛋白降解和过度的气道重塑,引起哮喘、肺气肿等许多呼吸系统疾病.     

MMP-2、MMP-9及其抑制剂TIMP-2、TIMP-1与肾脏疾病

肾脏细胞外基质(ECM)合成与降解失衡及其组织重塑导致的ECM积聚,是各种肾脏疾病发展至肾间质纤维化与肾小球硬化乃至终末期肾衰的共同病理表现.基质金属蛋白酶(MMP)是肾脏ECM降解的关键酶,金属蛋白酶组织抑制因子(TIMP)-2、-1分别为MMP-2、MMP-9内源性抑制剂.在不同类型的肾脏疾病或同一疾病的不同病理发...     

基质金属蛋白酶与小儿心血管疾病的关系

基质金属蛋白酶(MMPs)是一类锌、钙依赖性的蛋白水解酶家族,是细胞外基质降解的主要介质,MMPs的正常表达及MMPs/组织金属蛋白酶抑制剂(TIMPs)比例适当是维持心肌胶原纤维、心脏结构正常的重要因素,研究表明,许多小儿心血管疾病时MMPs的表达及活性过度增强或MMPs/TIMPs比例失调,参与了心脏组织的重构,引起心腔扩大,室壁变薄,导致心功能的进一步恶化.合理调控MMPs的表达和活性将有利于心功能的恢复.     

基质金属蛋白酶及其抑制剂与神经母细胞瘤

早期转移是神经母细胞瘤最为显著的生物学特征之一。降解细胞外基质是肿瘤浸润和转移过程中最为重要的一步，而基质金属蛋白酶又是降解细胞外基质的最重要的酶类，组织金属蛋白酶抑制剂是其天然抑制剂。许多研究已证实基质金属蛋白酶及其抑制剂的表达异常和比例失调与神经母细胞瘤的浸润和转移密切相关。抑制基质金属蛋白酶的活性成为抗神经母细胞瘤转移治疗的一个新靶点。     

基质金属蛋白酶及其抑制剂与神经母细胞瘤

早期转移是神经母细胞瘤最为显著的生物学特征之一。降解细胞外基质是肿瘤浸润和转移过程中最为重要的一步,而基质金属蛋白酶又是降解细胞外基质的最重要的酶类,组织金属蛋白酶抑制剂是其天然抑制剂。许多研究已证实基质金属蛋白酶及其抑制剂的表达异常和比例失调与神经母细胞瘤的浸润和转移密切相关。抑制基质金属蛋白酶的活性成为抗神经母细胞瘤转移治疗的一个新靶点。     

基质金属蛋白酶与小儿心血管疾病的关系

基质金属蛋白酶(MMPs)是一类锌、钙依赖性的蛋白水解酶家族，是细胞外基质降解的主要介质，MMPs的正常表达及MMPs／组织金属蛋白酶抑制剂(TIMPs)比例适当是维持心肌肢原纤维、心脏结构正常的重要因素，研究表明，许多小儿心血管疾病时MMPs的表达及活性过度增强或TIMPs／TIMPs比例失调，参与了心脏组织的重构，引起心腔扩大，室壁变薄，导致心功能的进一步恶化。合理调控MMPs的表达和活性将有利于心功能的恢复。     

支气管肺发育不良不同时期基质金属蛋白酶、基质金属蛋白酶特异性组织抑制物及核转录因子κB表达变化

目的研究基质金属蛋白酶(MMP-9)及其抑制剂基质金属蛋白酶特异性组织抑制物(TIMP-1)在支气管肺发育不良(BPD)患儿肺组织中的表达,探讨细胞外基质降解在BPD发病机制中的作用;同时进行肺组织核转录因子(NF—κB)活性研究,阐明MMP-9转录机制的调控。方法收集我院新生儿病房死亡患儿尸检肺组织标本共29例,分别行肺组织病理染色、MMP-9、TIMP-1和NF-κB免疫组织化学染色。根据临床诊断和尸检病理诊断分为2组:1.肺透明膜病(HMD)或BPD组: 25例,依据Dik分期标准,按死亡时日龄将其分为4期,急性期(11例)、再生期(7例)、过渡期(2例)和慢性期(5例);2.对照组: 即无肺部疾病者4例。结果BPD组MMP-9表达明显高于对照组,且BPD慢性期MMP-9/TIMP-1比值明显降低(P< 0.05);细胞核内NF—κB与MMP-9表达强度呈正相关(r=0 7419)。结论MMP-9/TIMP-1表达失衡造成细胞外基质降解发生变化为BPD的重要发病机制之一;NF—κB在上调MMP-9表达中起关键作用。     

基质金属蛋白酶与颅内感染

基质金属蛋白酶（MMPs）是一组锌钙依赖性蛋白水解酶家族,是分解细胞外基质的蛋白酶类中最重要的一类.近年来研究发现,MMPs广泛参与颅内感染的病理过程,在颅内感染中MMPs表达增加,降解细胞外基质和脑血管基底膜,损伤血脑屏障,提高血管通透性,引起血管源性脑水肿,参与中枢神经系统免疫反应,促进感染的病理生理过程.该文就MMPs及其在颅内感染中的作用进行综述.     

基质金属蛋白酶与支气管肺发育不良

基质金属蛋白酶(matrix metalloproteinases,MMPs)是一组锌离子(Zn2+)依赖的内肽酶家族,能特异性降解细胞外基质(extracellular matrix,ECM),并为基质金属蛋白酶组织抑制剂(tissue inhibitors ofmetalloproteinases,TIMPs)及细胞因子所调控。ECM过度沉积、肺间质纤维化是婴儿支气管肺发育不良(bronchopulmonary dysplasia,BPD)的主要病理改变,因此MMPs在肺发育和肺部疾病过程中发挥重要作用,本文就MMPs的生物学特性及其在BPD中的作用作一综述。一、MMPs的结构特点和分类M     

基质金属蛋白酶与心力衰竭

心力衰竭是儿科重要死亡原因之一。近年来研究发现细胞外基质合成与降解的失衡与心肌重塑、心力衰竭的发生密切相关。而细胞外基质合成与降解的平衡又取决于基质金属蛋白酶(MMPs)及其组织抑制物的平衡。研究发现心力衰竭时MMPs的表达和活性增高,及其组织抑制物的比例失调。     

Levels of matrix metalloproteinase-9 and its inhibitor in bronchoalveolar lavage cells of asthmatic children

Our objective was to investigate the role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and their cellular sources in childhood asthma. We used 12 controls and 16 asthmatic children. The levels of MMP-9 and TIMP-1 in bronchoalveolar lavage (BAL) cells of asthmatic children were measured immunocytochemically. The positive level index, defined as the percentage of positive-stained cells × average optical density, was used to assess the expressing levels of MMP-9 and TIMP-1. The percentages of eosinophils and mast cells in bronchoalveolar lavage fluid (BALF) of asthmatic children were increased. Levels of MMP-9 and TIMP-1 in BAL cell of asthmatic children were increased significantly at about 30- and 35-fold relative to the controls, respectively. These results suggest that both MMP-9 and TIMP-1 contribute to tissue remodeling. MMP-9, which mediates the degradation of extracellular matrix (ECM), is increased significantly in the early or acute stage and may play a role in ECM degeneration. Excessive TIMP-1 may be synthesized following MMP-9 production when the body tries to repair the damage, which results in excessive deposition of ECM component.     

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目的以肺泡灌洗液(BALF)中羟脯氨酸(HYP)、基质金属蛋白酶9(MMP-9)及其抑制物(TIMP-1)为观察指标,了解呼吸道异物吸入对气道损害、重建的影响。方法对2002年6月至2003年3月在浙江大学儿童医院住院的46例呼吸道异物患儿,按异物滞留体内时间分为3组(A组:<7d,B组:~30d,C组:>30d),对3组患儿的BALF进行细胞学分析,并对其中的HYP、MMP-9细胞阳性率和TIMP-1质量浓度进行测定。对照组为12例有异物吸入可疑病史,但最后排除的儿童。结果对照组与患儿组间细胞学计数差异无显著性(P>0.05),但肥大细胞仅在患儿BALF中发现。对照组及各组患儿的MMP-9细胞阳性率分别为33.3%、62.5%、80.0%和93.3%,TIMP-1细胞阳性率分别为16.3%、50.0%、80.0%和93.3%,总体差异均有显著性意义(P=0.006和P<0.001);各组间HYP差异有显著性意义(P<0.001)。结论气道异物促进MMP-9、TIMP-1及HYP的表达和分泌,提示气道异物可导致支气管肺组织破坏和重建,其程度与异物滞留时间有关。     

Expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in tissues with a diagnosis of childhood lymphoma

Matrix metalloproteinases (MMP) are enzymes involved in the reconfiguration of the microenvironment by means of degrading the extracellular matrix and have more than 20 subgroups containing zinc. Proteins that serve as the inhibitors of these enzymes are called tissue inhibitors of matrix metalloproteinase (TIMP). These enzymes have been shown to be active in a wide range of processes, from wound recovery to fetus development, heart diseases, and spread of malignant diseases. The aim of this study was to investigate whether there is a relationship between the type, stage, and prognosis of childhood lymphoma subjects and matrix metalloproteinase type-9 (MMP-9) and its inhibitor, tissue inhibitor of matrix metalloproteinase type-1 (TIMP-1). Paraffin blocks of childhood patients diagnosed with non-Hodgkin lymphoma (n = 23), Hodgkin lymphoma (n = 14), or reactive lymphadenopathy (n = 12) were retrospectively immunohistochemically stained with MMP-9 and TIMP-1 stains and whether there was a relationship between the degree of staining and the type, tumor stage, and prognosis of the disease was investigated. Moderate and high degrees of MMP-9 staining were detected in 94.6% of the lymphoma patient tissues and a slight TIMP-1 staining was detected in 21.6% of the lymphoma patient tissues. No relationship was observed between the degree of these staining patterns and the type, tumor stage, and prognosis of the disease. This study indicates that the equilibrium between MMP-9 and TIMP-1 is important in lymphomas in addition to all the physiological and pathologic events although MMP-9 and the TIMP-1 staining patterns are not related to the tumor stage, prognosis, and type of the disease. Larger series of patients are needed to determine the prognostic value of MMP-9 and TIMP-1 in childhood lymphoma.     

Expression of matrix metalloproteinases and their inhibitors in retinoblastoma

Tumor invasion is the critical step that could lead to metastasis in retinoblastoma (RB), a common childhood cancer. Matrix metalloproteinases (MMPs) degrade extracellular matrix, which is a crucial step involved in various stages of tumor progression, including tumor angiogenesis, tumor growth, and also local invasion and subsequent distant metastasis. We investigated the role of extracellular MMP inducer (EMMPRIN), MMP-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMPs): TIMP-1, TIMP-2 in RB and correlated clinicopathologically. Among 60 tumors, EMMPRIN was expressed in 40 (64%), MMP-2 in 41 (66%), MMP-9 in 38 (61%), TIMP-1 in 35 (56%), and TIMP-2 in 33 (53%) tumors. EMMPRIN was positive (3+) in 13 (39%) out of 33 tumors with invasion and was positive (3+) in only 1 (3%) out of 29 tumors without invasion. MMP-2 (P<0.0001) and MMP-9 (P<0.0001) were significantly positive (3+) in 7 (21%) and 12 (36%) out of 33 tumors with invasion, whereas positive (3+) in 3 (10%) and faint (1+) in 10 (34%) tumors, respectively, out of 29 tumors without invasion. TIMP-1 (P<0.0001) and TIMP-2 (P=0.04) were significantly positive (3+) in 7 (21%) and 10 (30%), respectively out of 33 tumors with invasion, whereas positive (3+) in only 1 (3%) tumor each out of 29 tumors without invasion. Immunoblotting of tumors confirmed the presence of EMMPRIN, MMPs, and TIMPs. In conclusion, both MMPs and TIMPs may be involved RB invasion and EMMPRIN could play a role in up-regulation of MMP-2 in invasive RB.     

Col-Ⅳ、LN、FN和MMP-9在不同时期婴幼儿型血管瘤中的表达和意义

目的 观察不同时期婴幼儿型血管瘤(infantile hemangioma,IH)中细胞外基质结构蛋白和基质金属蛋白酶-9 (matrix metalloproteinase-9,MMP-9)的表达和分布,探讨基质结构蛋白和MMP-9在IH中潜在的作用和意义.方法 收集手术切除的血管瘤标本,经HE染色和Glut-1免疫组织化学染色后确诊为IH;应用免疫组织化学染色MaxVision法检测各标本中Ⅳ型胶原(Col-Ⅳ)、层黏连蛋白(LN)、纤维连接蛋白(FN)和MMP-9的表达情况,通过ImagePro Plus 6.0图像分析软件测量各组织中阳性染色区域的平均光密度(IOD).按患儿年龄将标本分为年龄＜3个月龄组,≥3～6个月组,≥6～9个月组,≥9～12个月组和≥12个月龄组5组.比较不同年龄组IH中基质结构蛋白和MMP-9表达的差异.结果 按标准纳入的IH共34例,其中月龄＜3个月8例,≥3～6个月7例,≥6～9个月6例,≥9～12个月8例,≥12个月5例.观察免疫组织化学染色结果显示Col-Ⅳ、LN、FN和MMP-9在各年龄组中表达强度不同,比较IOD值显示IH组织中Col-Ⅳ在≥12个月龄组(84.90±12.48)的表达较其他各年龄组高,且与＜3个月龄组(55.10±16.06)、≥3～6个月组(56.96±22.66)、≥6～9个月组(51.60±20.38)比较差异有统计学意义(P＜0.05).LN在≥9～12个月组(80.04±29.36)IH中表达最高,分别与＜3个月龄组(38.02±9.88)、≥3～6个月组(68.62±16.19)、≥6～9个月组(60.67±10.72)、月龄≥12个月组(45.96±5.02)比较差异均有统计学意义(P＜0.05).FN在≥6～9个月组(62.86±15.41) IH中表达最高,分别与＜3个月龄组(32.36±19.79)、≥3～6个月组(43.04±19.78)、≥9～12个月组(36.25±11.19)、月龄≥12个月组(27.57±13.90)比较差异有统计学意义(P＜0.05).MMP-9在＜3个月龄组(73.23±18.19)IH组织中表达最高,并随年龄增长≥3～～6个月组(59.31±12.85)、≥6～9个月组(35.80±7.50)、≥9～12个月组(26.89±10.21)、月龄≥12个月组(24.04±10.00)逐渐下降,其中＜3个月龄组、≥3～6个月组IH与其他各组比较差异有统计学意义(P＜0.05).结论 不同时期IH组织中Col-Ⅳ、LN、FN和MMP-9的表达有差异,这种差异可能是影响IH增生和消退的重要因素.     

Type I collagenases in bronchoalveolar lavage fluid from preterm babies at risk of developing chronic lung disease

OBJECTIVE: To assess whether increased collagenolysis precedes severe chronic lung disease (CLD). METHODS: Matrix metalloproteinase-1 (MMP-1) and MMP-8 (enzymes that degrade type I collagen, the main structural protein of lung extracellular matrix) were measured by enzyme linked immunosorbent assay in 100 bronchoalveolar lavage samples taken during the first 6 postnatal days from 45 ventilated preterm babies < 33 weeks gestation. The median value for each baby was calculated. CLD was defined as an oxygen requirement after the 36th week after conception. RESULTS: MMP-8 levels in bronchoalveolar lavage fluid were higher (median 13 ng/ml) in 20 babies who developed CLD than in 25 without CLD (median 2 ng/ml). No MMP-1 was detected in any sample. CONCLUSIONS: MMP-8 can be detected in bronchoalveolar lavage fluid from preterm babies, and higher levels are found in those who later develop CLD. MMP-8 may contribute to lung injury that occurs as a prelude to CLD.     

Extracellular matrix turnover and disease severity in Anderson–Fabry disease

Background: Anderson–Fabry disease (AFD) is an inherited metabolic disease associated with premature death from cardiovascular and renal disease. Recent studies have shown that patients with AFD develop progressive left-ventricular (LV) remodelling. We hypothesized that patients with AFD have abnormal extracellular matrix (ECM) turn over compared with normal controls.
Methods and Results: Twenty-nine (mean age (±SD), 44.1±11.7 years; 15 male) consecutive patients with AFD and 21 age- and gender-matched controls (mean age, 39.7±11.3 years; 10 male) had serum analysed for matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP)-1 and -2 levels using an in-house enzyme-linked immunosorbent assay. MMP-9 levels were significantly elevated in patients compared with controls (mean difference from controls, 427.1 ng/ml, 95% CI, 252.1 – 602.2 ng/ml, p <0.001). There was a negative correlation between MMP-9 and fractional shortening (r = − 0.5, p =0.01). There were no differences in TIMP levels between patients and controls. There was no correlation between LV mass or maximal LV wall thickness and MMP-9 levels. There was a positive correlation between MMP-9 levels and the Mainz Severity Score Index (r = 0.5, p =0.01). These relationships remained significant, independently of gender and age-using stepwise linear regression analysis.
Conclusion: Patients with AFD have higher levels of MMP-9 compared with controls. MMP-9 levels correlated with clinical markers of disease severity suggesting that abnormal ECM turnover plays an important role in the pathogenesis of AFD. This in turn suggests that MMP-9 levels may be a useful circulating marker for disease severity and a surrogate marker for the response to enzyme replacement therapy.