Effect of CCK-8 on expression of MMPs/TIMP-1 in TNF-α-induced RSC-364 / 中国药理学通报

Aim To observe the influence of CCK-8 on expression of MMPs/TIMP-1 in TNF-α-induced rat fibroblast-like synovial cell line RSC-364.Methods The secretion levels of MMP-1, MMP-3, MMP-9 and TIMP-1 were determined using ELISA;MMP-3 and MMP-9 mRNA expressions were detected by RT-PCR.Results MMP-3 and MMP-9 could not be examined in RSC-364 incubated with CCK-8 and unstimulated RSC-364, which was able to product a little MMP-1, TIMP-1 and express even less MMP-3,-9 mRNA.CCK-8 inhibited the increase in MMP-1, MMP-3, MMP-9 secretion and MMP-3,-9 mRNA expression in TNF-α-induced RSC-364.TIMP-1 production was also increased in TNF-α-induced RSC-364.CCK-8 had no effect on TIMP-1 production in TNF-α-induced RSC-364, but was able to reduce the ratios of MMP-1, MMP-3, MMP-9 to TIMP-1.Conclusion The inhibitory effect of CCK-8 on MMPs activity may be related to the decrease of MMPs mRNA expression, MMPs secretion and the ratios of MMPs to TIMP-1 in TNF-α-induced RSC-364, which indicates that CCK-8 might be a possible regulator in the pathogenesis of rheumatoid arthritis.

Research on effect of Celastrus orbiculatus extract on inhibiting invasion and metastasis of human gastric cancer SGC-7901 cells by mediating matrix metalloproteinases group and their inhibitors / 中草药

Objective: To study the effect and the mechanism of Celastrus orbiculatus extract (COE) on inhibiting the invasion and metastasis of human gastric cancer SGC-7901 cells. Methods: The groups of different cells were set up, such as negative control group, COE with different concentration groups, and positive control group. The effects of COE on the cytotoxicity and proliferation of human gastric cancer SGC-7901 cells were determined by MTT assay. The effect of COE on the metastatic ability of human gastric cancer SGC-7901 cells in vitro was observed by invasion assay and migration assay. The effects of COE on the expression of matrix metalloproteinases (MMPs) and their inhibitors in human gastric cancer SGC-7901 cells were examined by Western blotting. After the treatment in different groups, mRNAs of MMP2, MMP9, tissue inhibitors of metalloproteinases (TIMPs), TIMP1, and TIMP3 in cells were detected by RT-PCR. Results: Compared with the negative control group, human gastric cancer SGC-7901 cells treated with COE at different concentration exhibited a dose-dependent growth inhibition. COE obviously reduced the migration and invasion potential of human gastric cancer SGC-7901 cells. In addition, the expression levels of MMP2 and MMP9 were dramatically suppressed by COE in a concentration-dependent manner, while the expression levels of TIMP1 and TIMP3 were raised. RT-PCR showed that mRNAs of TIMP1 and TIMP3 were raised with the increase of drug concentration. Conclusion: COE could significantly inhibit the invasion and metastasis of human gastric cancer SGC-7901 cells via an up-regulation of the expression levels of TIMP1 and TIMP3 and down-regulation of the expression levels of MMP-2 and MMP-9.

Metaloproteinasas de la matriz en Odontología y sus consideraciones desde el campo de la química computacional / Matrix metalloproteinases and their considerations in Dentistry from the field of computational chemistry

Las metaloproteinasas de la matriz son una familia de proteasas zinc-dependientes encargadas de la remodelación de los componentes proteicos de la matriz extracelular de todos los tejidos, su actividad catalítica es controlada por inhibidores tisulares de metaloproteinasas de la matriz. En condiciones patológicas se pierde el equilibrio existente entre MMPs con respecto a la de estos inhibidores endógenos, este desequilibrio es evidente en enfermedades orales como la caries dental, gingivitis, periodontitis, entre otras, por lo tanto la posibilidad de lograr una inhibición selectiva de la actividad de estas enzimas con inhibidores sintéticos constituye un enfoque prometedor en el tratamiento de distintas enfermedades de la cavidad oral. Se presenta a continuación una revisión bibliográfica cuyo objetivo es analizar el papel que juegan las metaloproteinasas de la matriz en el desarrollo de patologías orales e identificar el aporte que ha hecho el análisis computacional de estas enzimas en el campo de la odontología. Para tal fin se llevó a cabo una búsqueda de la literatura disponible en bases de datos como Pubmed, Sience Direct, Ovid y Ebsco Host empleando palabras claves como: patologías orales, cáncer oral, adhesión dentinaria, metaloproteinasas de la matriz, inhibidor sintético de metaloproteinasas y modelado molecular. Se seleccionaron 35 artículos para orientar la presente revisión. Al terminar se pudo concluir que existe correlación positiva entre la desregulación de determinadas MMPs y la progresión de ciertas enfermedades orales, esto ha impulsado la identificación y el diseño insílico de inhibidores efectivos para estas proteínas, partiendo de análisis relación estructura-actividad y acoplamiento molecular computacional. Hasta la fecha se ha logrado demostrar que los inhibidores de MMPs más potentes presentan grupos hidroxamatos. Teniendo en cuenta lo anterior, el diseño de compuestos que bloqueen la actividad representa una estrategia quimiopreventiva racional encaminada a la inhibición de las MMPs(AU)

Matrix metalloproteinases are a family of zinc-dependent proteases responsible for the remodeling the protein components of extracellular matrix of all tissues; its catalytic activity is controlled by tissue inhibitors of matrix metalloproteinases. At pathological conditions the balance between MMPs regarding these endogenous inhibitors is lost, this imbalance is evident in oral diseases including dental caries, gingivitis, periodontitis, among others, hence the possibility of achieving selective inhibition of activity of these enzymes with synthetic inhibitors is a promising approach in the treatment of various diseases of the oral cavity. A literature review aimed at analyzing the role of matrix metalloproteinases in the development of oral diseases and identify the contribution made by the computational analysis of these enzymes in the field of dentistry is presented below. To this end a search of the literature available was conducted in databases such as Pubmed, Sience Direct, Ovid, and Ebsco Host using keywords like: oral pathology, oral cancer, dentin bonding, matrix metalloproteinases, synthetic inhibitor of metalloproteinases, and molecular modeling. 35 items were selected to guide this review. At the end it was concluded that there is positive correlation between deregulation of certain MMPs and progression of certain oral diseases, this has boosted in silico identifying and designing effective inhibitors for these proteins, based on structure-activity relationship analysis and molecular docking computational. To date it has successfully demonstrated that the most potent inhibitors of MMPs have hydroxamate groups. So far it has successfully demonstrated that the most potent inhibitors of MMPs have hydroxamate groups. Considering the above, the design of compounds that block the chemopreventive activity represents a rational strategy for the inhibition of MMPs(AU)

Análise da expressão das metaloproteinases e seus inibidores teciduais no músculo detrusor de pacientes com obstrução infravesical por hiperplasia prostática benigna / Expression of metalloproteinases and their tissue inhibitors in the detrusor muscle of patients with bladder outlet obstruction due to benign prostatic hyperplasia

Introdução: A obstrução infravesical (OIV) de longo prazo secundária a hiperplasia prostática benigna (HPB) pode causar alterações funcionais e morfológicas na bexiga. Um dos principais eventos consiste no aumento da deposição de colágeno e perda de complacência vesical, levando a alteração de armazenamento e esvaziamento urinário. O aumento da deposição de colágeno na matriz extracelular (MEC) da musculatura detrusora é a principal razão para a diminuição da complacência vesical. Na bexiga, assim como em outros órgãos, este fenômeno depende da atividade equilibrada de enzimas proteolíticas, incluindo as metaloproteinases (MMP) e os seus inibidores endógenos (inibidores teciduais de metaloproteinases-TIMPs). Como estes fenômenos são desconhecidos na bexiga obstruída, o objetivo deste estudo foi avaliar a expressão gênica de colágeno, MMPs e seus inibidores na bexiga de pacientes com obstrução infravesical. Material e Métodos: Foi realizada uma análise prospectiva e controlada de 43 pacientes com OIV devido a HPB, que foram submetidos à ressecção transuretral da próstata (RTUP) entre 2011 e 2012. Como grupo controle foram selecionados espécimes de músculo detrusor de 10 pacientes que foram submetidos a prostatectomia radical retropúbica devido adenocarcinoma de próstata. Todos estes pacientes tinham idade menor que 60 anos, tamanho de próstata menor que 30 gramas ao ultra-som e escore internacional de sintomas prostáticos (IPSS) menor que 7. Todos os pacientes foram submetidos a estudo urodinâmico pré e pós operatório (após 6 meses). A biópsia de fragmento de músculo da bexiga foi realizada ao final da RTUP e colocada em solução estabilizadora de RNA para quantificação da expressão de colágenos I e III, metaloproteinases de matriz 1, 2 e 9, e inibidores de MMPs (TIMP1, TIMP2 e RECK) na bexiga de pacientes com HPB. Os genes descritos foram avaliados através da técnica de reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR)....

Introduction: Long-term Bladder outlet obstruction (BOO) secondary to Benign prostatic Hyperplasia (BPH) can cause functional and morphological abnormalities in the bladder, such as increased collagen deposition and loss of compliance, leading to urinary storage and voiding symptoms. A decrease in bladder compliance is known to be correlated with deterioration of renal function. Increased deposition of collagen in the extracellular matrix (ECM) is the primary reason for a decreased compliance. In the bladder, as in other organs, this phenomenon is dependent on the balanced activity of proteolytic enzymes, including matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). The imbalance between MMPs and TIMPs is a key regulator in ECM turnover. Since these mechanisms are unknown in the obstructed bladder, the objective of this study was to evaluate gene expression of collagen, MMPs and their inhibitors in patients with bladder outlet obstruction due to BPH. Material and Methods: We performed a prospective and controlled analysis of 43 patients with BOO due to BPH who underwent transurethral resection of the prostate (TURP) from 2011 to 2012. The control group was comprised of 10 bladder specimens from patients with < 60 years who underwent radical prostatectomy with an International Prostatic Symptom Score (IPSS) < 8 and prostate volume < 30 grams. All patients underwent urodynamic analysis pre and post operatively after 6 months. A biopsy of the bladder muscle was performed at the end of TURP for analysis of collagen, metalloproteinases and TIMPs gene expressions. For this purpose we used the quantitative real time polymerase chain reaction method (qRT-PCR)...

Effect of carvedilol on cardiac metalloproteinases and tissue inhibitors of metalloproteinases after myocardial infarction in rats / 第二军医大学学报

Objective: To investigate the effect of carvedilol on expression of cardiac matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) after myocardial infarction in rats. Methods: An animal model of acute myocardial infarction (AMI) was established by descending left coronary artery ligation in 24 rats and they were divided into carvedilol (10 mg • kg-1 • d-1) group (n=12) and normal saline group (n=12). Sham-operated group (n=9) received the same procedure but with no ligation. All animals were treated for 6 weeks via a gastric lavage. Heart function and hemodynamic parameters were determined after 6 weeks. The protein expression of cardiac MMP-2, MMP-9 and TIMP-2 was detected by immunohistochemical analysis in AMI groups, and the MMPs activities were assessed by zymography. Gene expression of myocardial MMPs/TIMPs (MMP-2,-9 and TIMP-1, -2) and cytokines (TNF-α, IL-1β) were measured by real-time quantitative PCR. Results: Compared with Sham-operated group, carvedilol group had significantly higher left ventricular end-diastolic pressure (LV-EDP) and lower LV upstroke velocity (+dp/dtmax) and LV descent velocity (- dp/dtmax) (P<0.01). Activities of MMP-2 and MMP-9, protein expression of MMP-2, MMP-9 and TIMP-2, and mRNA expression of MMP-2, MMP-9, TIMP-1, TIMP-2, IL-1β, and TNF-α were all higher in carvedilol group compared with sham-operated group (P<0.05). Compared with normal saline group, carvedilol group had lower LVEDP(P

Differential Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Thioacetamide-Induced Chronic Liver Injury

Hepatic fibrogenesis, a complex process that involves a marked accumulation of extracellular matrix components, activation of cells capable of producing matrix materials, cytokine release, and tissue remodeling, is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The MMP-TIMP balance can regulate liver fibrogenesis. The aim of this study was to evaluate the expression patterns of MMPs and TIMPs during thioacetamide (TAA)-induced liver fibrogenesis. Chronic liver injury was induced with TAA (200 mg/kg i.p.) for 4 or 7 weeks in male Sprague-Dawley rats. Hepatic injury and fibrosis were assessed by hematoxylin-eosin (H&E) staining, and collagen deposition was confirmed by Sirius Red staining. The level of hepatic injury was quantified by serological analysis. The transcriptional and translational levels of alpha-smooth muscle actin (alpha-SMA), MMPs, and TIMPs in the liver were measured by Western blotting, RT-PCR, and immunohistochemistry. MMP, TIMP, and alpha-SMA were observed along fibrotic septa and portal spaces around the lobules. TAA treatment increased transcription of both MMPs and TIMPs, but only TIMPs showed increased translation. The dominant expression of TIMPs may regulate the function of MMPs to maintain liver fibrosis induced by TAA.

A Influência das Metaloproteinases da Matriz (MMPs) na Doença Periodontal e Perimplantar: [revisão] / The Influence of The Matrix Metalloproteinases (MMPs) in Periodontal and Peri-Implantar Disease: [review]

As metaloproteinases da matrix (MMPs) são consideradas as proteinases primárias envolvidas na destruição dos tecidos periodontais, através da degradação de moléculas da matriz extracelular. Na presença da doença periodontal e perimplantar, os níveis dessas enzimas se elevam e podem alterar o curso da resposta inflamatória ao redor dos dentes e impantes. O objetivo deste trabalho foi realizar uma revisão da literatura, considerando a importância das metaloproteinases da matriz na modulação da resposta inflamatória nos tecidos periodontais e perimplantares.

The matrix metalloproteinases are considered fundamental proteinases involved into destruction of periodontal tissues, through degradation of extracellular matrix proteins. In the presence of periodontal and peri-implantar disease, the enzymes levels increase and may change the path of inflammatory activity surrounding the teeth and peri-implants. The purpose of this study was to practice a literature review, compairing matrix metalloproteinases and their importance in the modulation of the inflammatory activity involved in periodontal and peri-implantar disease.

Expression of MMP-9, TIMP-1 and CA125 in ectopic and eutopic endometrium of adenomyosis treated with Chinese Medicine / 西安交通大学学报(医学版)

Objective To study the mechanism of Chinese Medicine in treating adenomyosis. Methods Thirty-seven patients in the Chinese Medicine treated group (17 cases of adenomyosis) and the control group (20 cases of adenomyosis, non-drug treated) underwent hysterectomy. Endometrium was looked as eutopic endometrium and adenomyosis as ectopic endometrium. Expression of MMP-9 and TIMP-1 in eutopic and ectopic endometrium were measured by immunohistochemical techniques. Meanwhile the levels of CA125 in serum were measured. Results The ectopic endometrium of the Chinese Medicine treated group expressed lower level of MMP-9, higher level of TIMP-1 and lower ratio of MMP-9/TIMP-1 than the ectopic endometrium of the control group (P<0.05). The levels of CA125 in serum were significantly decreased in Chinese Medicine group after treated as contrast with those in control group. Conclusion Chinese Medicine could reduce the level of CA125 and the ratio of MMP-9 and TIMP-1 to prevent the progression of adenomyosis.

Expression of MMP-9 and TIMP-1 in ectopic and eutopic endometrium of adenomyosis treated with mifepristone / 上海第二医科大学学报

Objective To study whether the mechanism of mifepristone in treating adenomyosis is suppressing matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1(MMP-9/TIMP-1). Methods Thirty-five patients in the mifepristone treated group(19 cases of adenomyosis) and the control group(16 cases of adenomyosis,non-drug treated) underwent hysterectomy.Endometrium was looked as eutopic endometrium and adenomyosis as ectopic endometrium.Expression of MMP-9 and TIMP-1 in eutopic and ectopic endometrium were measured by immunohistochemical techniques. Results The ectopic endometrium of the mifepristone treated group expressed lower level of MMP-9,higher level of TIMP-1 and lower ratio of MMP-9/TIMP-1 than the ectopic endometrium of the control group(P

TGF-beta1 Transgenic Mouse Model of Thoracic Irradiation: Modulation of MMP-2 and MMP-9 in the Lung Tissue / 华中科技大学学报（医学）（英德文版）

To investigate the effects of TGF-β1 on the two gelatinases (MMP-2 and MMP-9), and their roles in lung remodeling after irradiation-induced lung injury. Expressions of TGF-β1 were measured with western blot, and expressions of MMP-2 and MMP-9 were analyzed with zymography in a TGF-β1 transgenic mouse model after thoracic irradiation with 12 Gy. We found expressions of TGF-β1 in the lung from the transgenic mice were three folds as compared to those from control mice. With densitometrical analysis, we found a significant decrease in MMP-9 activity in lung homogenates from the transgenic mice as compared with those from non-transgenic control mice 8 weeks after sham-irradiation (relative MMP-9 activity: C: 1.000±0.1091; TG: 0.4772± 0.470 (n=8, P＜0.05). But MMP-2 was constitutively expressed in the lung homogenates from the transgenic mice as compared to those from control mice 8 weeks aftersham-irradiation (relative MMP-2 activity 8 weeks after sham-irradiation: C: 1.000±0.1556, TG: 1.0075±0.1472). Eight weeks after thoracic irradiation with 12 Gy, we observed a significant increase of MMP-2 and MMP-9 activity in lung homogenates from both transgenic and normal mice. In TGF-β1 transgenic mice relative MMP-9 activity was increased to 1.5321±0. 2217 folds 8 weeks after thoracic irradiation with 12 Gy as compared to those after sham-irradiation (1.000±0.2153), and relative MMP-2 activity was increased to 1. 7142±0. 4231 folds. Our results show that TGF-β1 itself down-regulates activity of MMP-9, thereby decreases ECM degradation in lungs of TGF-β1 transgenic mice.Also we find that ionizing irradiation upregulates both MMP-2 and MMP-9 activity. Over-expressions of MMP-9 and MMP-2 after lung irradiation are involved in the inflammatory response associated with radiation-induced lung injury, and maybe further in radiation-induced lung fibrosis.

Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gingival and periodontal ligament fibroblasts treated with lipopolysaccharide from Prevotella intermedia / 대한치주과학회지

Matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes and implicated in the remodeling and degradation of extracellular matrix under both physiological and pathological conditions. Connective tissue degradation in periodontal diseases is thought to be due to excessive MMP activities over their specific inhibitors. The effects of lipopolysaccharide (LPS) from Prevotella intermedia, one of the major putative pathogens of periodontitis, on the expression of mRNA for MMPs and tissue inhibitors of metalloproteinases (TIMPs) in human gingival and periodontal ligament fibroblasts were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of mRNAs encoding MMP-1, -2, -3, -10, and -14 was increased in human gingival fibroblasts treated with P. intermedia LPS, whereas MMP-11 and TIMP-2 mRNA expression was decreased in these cells stimulated with LPS. P. intermedia LPS increased the MMP-1, -2, -10, -11, and -14 mRNA expression and decreased TIMP-1 and -2 mRNA expression in human periodontal ligament fibroblasts. These findings imply that P. intermedia LPS may play an important role in the connective tissue degradation in periodontitis.

Expression of Matrix Metalloproteinases and Their Endogenous Inhibitors in Human Abdominal Aortic Aneurysms

PURPOSE: Among the theories in the pathogenesis of abdominal aortic aneurysms, matrix metalloproteinase (MMP)- induced excessive degradation of extracellular matrix protein has been widely recognized. Normally, MMPs keep a balance with their endogenous tissue inhibitors of metalloproteinases (TIMPs). Recently, the MMP-TIMP imbalance has been investigated for potential etiological role in AAA formation. The aim of this study was to define the role of the imbalance between the expressions of the specific MMPs and their physiologic inhibitors (TIMPs) in the formation of human abdominal aortic aneurysm (AAA). METHODS: Aortic tissues from 12 patients with AAAs, 4 age-matched patients with aortoiliac occlusive diseases (AODs), and 6 cadaveric organ donors, as normal controls, were obtained and prepared. The productions and expressions of MMP-2, 9, MT1-MMP and TIMP-1, 2, and 4 were analyzed using gelatin zymography, Western blotting, and immunohistochemistry. RESULTS: In the gelatin zymography, the net matrix-degrading activities were higher in the AAAs and AODs than in the normal control group due to the higher presence of MMP-2 and 9. From the Western blot analysis and immunohistochemistry, those with AAAs and AODs showed significantly higher expressions of MMP-2, 9, and MT1-MMP than the normal control group. However, no differences in the TIMP-1 and 2 expressions were found between the all groups. In contrast, TIMP-4 protein was expressed at a significantly lower level in the AAAs and AODs than in the normal control group. MMP-9/TIMP-1, MMP-2/TIMP-2, and MMP-2/TIMP-4 were significantly different between AAAs and normal control group. From the densitometric analysis of the Western blotting, no significant differences were found in tissue expressions of MMPs and TIMPs between the AAAs and AODs groups, but, in the immunohistochemistry, the AAAs group showed a different distribution of the MMP expression confined to sites of overt medial damage compared with that in the intimal plaque in AODs. CONCLUSION: The imbalance of expression between specific MMPs and their endogenous inhibitors plays an etiological role in the formation of AAAs. In addition, TIMP-4 may suppress the MMP-induced aneurysmal formation. Our results suggest that the eventual formation of aneurysms or occlusive lesions appears not to result from an ongoing difference in the proteolytic activities, but from differences in other factors, as-yet-undefined, including the distribution of MMPs expression within the aortic walls.

Expression of MMP-9,TIMP-1 and CA125 in ectopic and eutopic endometrium of adenomyosis treated with Chinese Medicine / 西安交通大学学报(医学版)

Objective To study the mechanism of Chinese Medicine in treating adenomyosis.Methods Thirty-seven patients in the Chinese Medicine treated group(17 cases of adenomyosis) and the control group(20 cases of adenomyosis,non-drug treated) underwent hysterectomy.Endometrium was looked as eutopic endometrium and adenomyosis as ectopic endometrium.Expression of MMP-9 and TIMP-1 in eutopic and ectopic endometrium were measured by immunohistochemical techniques.Meanwhile the levels of CA125 in serum were measured.Results The ectopic endometrium of the Chinese Medicine treated group expressed lower level of MMP-9,higher level of TIMP-1 and lower ratio of MMP-9/TIMP-1 than the ectopic endometrium of the control group(P

Tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1 and TIMP-2) mRNA and antigens location in the liver of patients with cirrhosis / 中华传染病杂志

Objective To study the expression and distribution of TIMP 1 and TIMP 2 in liver tissue of cirrhosis patient and to investigate the roles and pathogenesis of TIMP 1 and TIMP 2 in liver cirrhosis. Methods TIMP 1 and TIMP 2 proteins and mRNA were detected with immunohistochemistry and in situ hybridization methods using monoclonal antibodies and cDNA probes. Results mRNA and proteins of TIMP 1 and TIMP 2 were detected in all the liver tissues from 40 liver cirrhosis patients, all in cytoplasm but not nucleus. TIMP 1 and TIMP 2 were found co exist in all samples, while TIMP 1 concentration was higher. Conclusions mRNA and protein of TIMP 1 and TIMP 2 are found in all the cirrhosis patient samples. Liver TIMP 1 and TIMP 2 concentrations increase with the progression of liver cirrhosis, decrease the degradation of extracellular matrix proteins, resulting in the initiation and the development of liver fibrosis and liver cirrhosis.

Role of tissue inhibitors of metalloproteinases (TIMPs) in colorectal carcinoma

Increased production of matrix metalloproteinases (MMPs) has been associated with increases in invasive and metastatic potential in many types of human carcinoma. Tissue inhibitors of metalloproteinase (TIMP)-1 inhibits most interstitial collagenases and MMP-9. TIMP-2 binds specifically and noncovalently to the pro-form of MMP-2 and inhibits its enzyme activity. In this study, we examined TIMP-1 and TIMP-2 expressions in relation to clinicopathological variables in colorectal carcinoma with in situ hybridization and immunohistochemistry. TIMP-1 and TIMP-2 expressions were localized overwhelmingly to pericancer stromal cells, while malignant and normal mucosal cells were weak or negative. Strong stromal TIMP-1 immunoreactivity correlated with Dukes' stage (p=0.022), status of lymph node metastasis (p=0.044) and poor survival (p= 0.005). The degree of immunohistochemical staining of TIMP-2 did not correlate with all clinicopathological variables. The correlation between enhanced TIMP-1 expression and advanced stage and poor survival suggest a growth promoting activity of TIMP-1 in colorectal carcinoma.

Effect of high glucose on the expression of matrix metalloproteinase 2 and its inhibitors in human peritoneal mesothelial cells / 中华肾脏病杂志

Objective To study the gene and protein expression of matrix metalloproteinase 2 (MMP2) and its inhibitors TIMP1 and TIMP2 in human peritoneal mesothelial cells (HPMC), and the possible role of high glucose in submesothelial extracellular matrix (ECM) degradation during peritoneal dialysis (PD) . Methods Primary HPMC was isolated from spent peritoneal dialysis effluent collected from PD patients. After HPMC confluence, the cells were detached by trypsinization and passaged into 25 cm2 tissue-culture flasks. The effect of high glucose and hyperosmolarity on the gene expression of MMP2, TIMP1 and TIMP2 in HPMC was studied by semi-quantitative RT-PCR. Immunohistochemistry and zymography were used to measure the protein expression of MMP/TIMP in HPMC. Results HPMC expressed MMP2, TIMP1, TIMP2 at both gene and protein levels. 4. 25% glucose significantly up-regulated TIMP1 gene expression in HPMC( P

Immunodetections of the Metalloproteinase (MMP-2 and MMP-9) and Tissue Inhibitor of Metalloproteinases (TIMP-2) in Prostatic Adenocarcinomas / 대한암학회지

PURPOSE: The metalloproteinases (MMP) and their inhibitors (TIMP) have been suggested to play a role in tumor invasion and metastasis. There have been some dispute on the exact role of TIMP and MMP in tumor progression. The purpose of this study is to prove TIMP expression in relation with prevention of tumor progression including invasion or metastasis with MMP expression. MATERIALS AND METHODS: We have performed immunohistochemical staining of MMP-2, MMP-9 and TIMP-2 on 15 cases of benign prostatic hyperoplasia (BPH), and 30 cases of prostatic carcinomas which were classified as angio or neural invasion positive (PC-2) and negative group (PC-1). RESULTS: MMP-2, MMP-9, and TIMP-2 were not detected in BPH. PC-2 pateints had higher levels of collagenases than BPH, while PC-1 patients had higher levels of TIMP-2 and lower levels of MMP-2, MMP-9 than PC-2. Expression of TIMP-2 were inversely proportional to collagenases. CONCLUSION: We conclude that highly invasive prostatic carcinoma (PC-2) contained relatively high levels of MMP-2, MMP-9 and low amounts of TIMP-2. These results are discussed with respect to the possible role of MMPs and TIMP in prostatic tumor progression.

Effect of carvedilol on cardiac metalloproteinases and tissue inhibitors of metalloproteinases after myocardial infarction in rats / 第二军医大学学报

Objective:To investigate the effect of carvedilol on expression of cardiac matrix metalloproteinases(MMPs)and tissue inhibitors of metalloproteinases(TIMPs)after myocardial infarction in rats.Methods:An animal model of acute myocar- dial infarction(AMI)was established by descending left coronary artery ligation in 24 rats and they were divided into carvedilol (10 mg?kg~(-1)?d~(-1))group(n=12)and normal saline group(n=12).Sham operated group(n=9)received the same proce- dure but with no ligation.All animals were treated for 6 weeks via a gastric lavage.Heart function and hemodynamic parame- ters were determined after 6 weeks.The protein expression of cardiac MMP-2,MMP-9 and TIMP-2 was detected by immuno- histoehemical analysis in AMI groups,and the MMPs activities were assessed by zymography.Gene expression of myocardial MMPs/TIMPs(MMP-2,9 and TIMP-1,2)and cytokines(TNF-?,IL-1?)were measured by real-time quantitative PCR.Re- suits:Compared with Sham-operated group,earvedilol group had significantly higher left ventricular end-diastolic pressure(LV- EDP)and lower LV upstroke velocity(+dp/dt_(max))and LV descent velocity(-dp/dt_(max))(P