OBJECTIVETo study the relationship between atrial structural remodeling and the expressions of matrix metalloproteinase (MMPs) and their tissue inhibitors (TIMPs) in atrial fibrillation (AF).

METHODSBiopsy samples of the right atrial appendages were collected from 20 patients with sinus rhythm and 30 with AF undergoing heart valve replacement surgery for rheumatic heart diseases. All the patients received echocardiographic examination preoperatively. MMP-1, -3, -7, -9 and TIMP-1, -2, -3, -4 protein expressions were detected by immunohistochemistry and RT-PCR.

RESULTSCompared with those in patients with sinus rhythm, the AF patients had significantly increased left and right atrial diameters and mRNA levels of MMP-3, -7, -9 and TIMP-1, -2, -3, -4 (P<0.01). MMP-1 expression also showed an increase in AF patients, but the difference was no statistically significant from that in patients with sinus rhythm.

CONCLUSIONThe expressions of MMP-1, -3, -7, -9 and TIMP-1, -2, -3, -4 increase in fibrillating atrial tissue, which may contribute to atrial structural remodeling and atrial dilatation in AF patients.

Adult ; Aged ; Atrial Fibrillation ; enzymology ; pathology ; physiopathology ; Female ; Humans ; Male ; Matrix Metalloproteinases ; genetics ; metabolism ; Middle Aged ; Tissue Inhibitor of Metalloproteinases ; genetics ; metabolism

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Tissue Inhibitor of Metalloproteinase-2/genetics ; RNA, Messenger/metabolism ; Matrix Metalloproteinases, Membrane-Associated ; Matrix Metalloproteinases/*genetics ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 1/genetics ; Humans ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Enzymologic ; Female ; Carcinoma, Ductal, Breast/genetics/*physiopathology ; Carcinoma in Situ/genetics/*physiopathology ; Breast Neoplasms/genetics/*physiopathology

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Tissue Inhibitor of Metalloproteinase-2/genetics ; RNA, Messenger/metabolism ; Matrix Metalloproteinases, Membrane-Associated ; Matrix Metalloproteinases/*genetics ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 1/genetics ; Humans ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Enzymologic ; Female ; Carcinoma, Ductal, Breast/genetics/*physiopathology ; Carcinoma in Situ/genetics/*physiopathology ; Breast Neoplasms/genetics/*physiopathology

The degradation of arthrodial cartilage is a typical characteristic in the pathogenesis of osteoarthritis. matrix metalloproteinases (MMPs) are the primary enzymes involved in extracellular matrix degradation of cartilage. The mechanism of MMPs in extracellular matrix degradation of cartilage is becoming clear with the in-depth study about MMPs, such as activation, activity regulation, related signal transduction pathways and transcription factors. This artice reviewed the activation, expression and regulation of MMPs in the related theory and empirical study of osteoarthritis cartilage.
Cartilage ; enzymology ; Enzyme Activation ; Gene Expression Regulation, Enzymologic ; Humans ; Matrix Metalloproteinases ; genetics ; metabolism ; Multigene Family ; Osteoarthritis ; enzymology ; genetics ; Signal Transduction

The suitable experimental animal model is important in research of pathogenesis and therapeutic strategies of diabetic foot ulcer, and the murine model is the most commonly used one at present. It can be divided into two types: the animal model simulating pathological conditions and the model simulating clinical symptoms. This article reviews the current research progress on the mechanisms of diabetic ulcer pathogenesis, and relevant treatment strategies, including the inhibition of matrix metalloproteinases (MMPs) expression, promotion of angiogenesis and anti-inflammatory therapy.
Animals ; Anti-Inflammatory Agents ; therapeutic use ; Diabetic Foot ; etiology ; genetics ; therapy ; Disease Models, Animal ; Humans ; Matrix Metalloproteinase Inhibitors ; therapeutic use ; Matrix Metalloproteinases ; genetics ; metabolism ; Mice ; Neovascularization, Physiologic ; physiology

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.
Animals ; Collagen/metabolism ; Extracellular Matrix/chemistry/metabolism ; *Liver Cirrhosis/chemically induced/metabolism/pathology ; Male ; Matrix Metalloproteinases/genetics/*metabolism ; Rats ; Rats, Sprague-Dawley ; Thioacetamide/*toxicity ; Tissue Inhibitor of Metalloproteinases/genetics/*metabolism

BACKGROUNDReceptor interacting protein 1 (RIP1), which plays a key role in apoptosis, cell survival and programmed cell necrosis, is one of the most important proteins in the RIP family. The purpose of this study was to investigate the roles of RIP1 in the apoptosis, the generation of reactive oxygen species (ROS) and the expression of matrix metalloproteinases (MMPs) induced by ultraviolet B (UVB) in fibroblasts.

METHODSsiRNA targeting RIP1 was used to silence RIP1 expression in the NIH3T3 fibroblasts. The mRNA and protein levels of MMP-1 and MMP-3, caspase-3 and -8 activities, and ROS activities were determined by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), immunoblotting, caspase activity assay, immunofluorescence, and flow cytometry.

RESULTSThe mRNA and protein expressions of MMP-1 and MMP-3 were significantly increased in RIP1 deficient NIH3T3 cells at 24 hours after UVB treatment. At 24 hours after exposure to UVB, RIP1 deficient NIH3T3 cells presented apoptotic morphology, and the apoptosis rate was significantly increased accompanied by pronounced increase in caspase-8 and -3 activities. ROS production was inhibited by UVB at 12 hours in RIP1 deficient NIH3T3 cells.

CONCLUSIONRIP1 is involved in NIH3T3 cell damage induced by UVB via participating in the apoptosis, expression of MMPs and ROS production.

Animals ; Apoptosis ; GTPase-Activating Proteins ; genetics ; metabolism ; Matrix Metalloproteinase 1 ; genetics ; metabolism ; Matrix Metalloproteinase 3 ; genetics ; metabolism ; Matrix Metalloproteinases ; genetics ; metabolism ; Mice ; NIH 3T3 Cells ; RNA, Small Interfering ; Reactive Oxygen Species ; metabolism ; Ultraviolet Rays

Animals ; Liver Cirrhosis ; enzymology ; Male ; Matrix Metalloproteinases, Secreted ; biosynthesis ; genetics ; Mice ; RNA, Messenger ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics

OBJECTIVETo study the relationship between activation of pro-MMP-2 and expression of matrix metalloproteinases (MMP)-2, MT1-MMP and tissue inhibitor of metalloproteinases (TIMP)-2 mRNA in thymoma and thymic carcinoma; and to study the molecular mechanism of invasion and metastasis of thymic epithelial tumors.

METHODSFresh tissue specimens of thymoma, thymic carcinoma and normal thymus were included. The mRNA expression of MMP-2, MT1-MMP and TIMP-2 were analyzed by real-time reverse transcription polymerase chain reaction. The pro-MMP-2 activation ratio and its localization were determined by gelatin zymography and film in-situ gelatin-Zymography, respectively. Correlation of mRNA expression of MMP-2, MT1-MMP and TIMP-2 was investigated in tumors with different histological subtypes and clinical stages.

RESULTSThere were no significant differences in the expressions of MMP-2, MT1-MMP and TIMP-2 mRNA between I and II stage or III and IV stage thymomas (P > 0.05). However, significant differences of the expressions were observed between three tumor groups: I-II stage, III-IV stage and thymic carcinomas (P < 0.005), and between three histological subtypes: AB-B1 (lymphocyte-rich and mixed types), B2-B3 (cortical and predominantly polygonal cells types) and thymic carcinomas (P < 0.05). Expression levels of MT1-MMP and TIMP-2 mRNA were correlated with pro-MMP-2 activation ratio (Spearman rank correlation: r = 0.7235, r = 0.7647, P < 0.005). The expression of MMP-9 did not show significant differences between thymomas and thymic carcinomas.

CONCLUSIONSMMP-2, MT1-MMP and TIMP-2 mRNA expression levels are correlated with the histologic subtypes and clinical stages of thymoma. The mRNA expressions of MT1-MMP and TIMP-2 are correlated with the activation ratio of pro-MMP-2. It is speculated that upregulation of MT1-MMP gene expression may induce an activation of pro-MMP-2 through TIMP-2.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; enzymology ; metabolism ; pathology ; Enzyme Activation ; Female ; Humans ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinases ; biosynthesis ; genetics ; Matrix Metalloproteinases, Membrane-Associated ; Middle Aged ; Neoplasm Staging ; RNA, Messenger ; biosynthesis ; genetics ; Thymoma ; classification ; enzymology ; metabolism ; pathology ; Thymus Gland ; enzymology ; metabolism ; Thymus Neoplasms ; classification ; enzymology ; metabolism ; pathology ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics

OBJECTIVETo construct differential expression profiles of adenoid cystic carcinoma cell lines for screening candidate genes related to metastasis and to verify some candidate genes in adenoid cystic carcinoma.

METHODSRestriction fragments differential display PCR (RFDD-PCR) was used to set up gene expression profiles of adenoid cystic carcinoma cell lines-ACC-M and ACC-2, with high and low metastasis potential respectively. Candidate genes were screened through bioinformatics analysis. Then, a gene family of these candidate genes was checked using semi-quantitative reverse transcription-PCR(RT-PCR).

RESULTSTwo gene expression profiles including 5420 gene fragments were constructed, 12 genes of a family called matrix metalloproteinase genes (MMPs) were observed obvious differentially expressed between two cell lines. Results of semi-quantitative RT-PCR also identified this different expression of MMP2,MMP7,MMP9,MMP14,MMP15 and MMP24.

CONCLUSIONThe construction of gene expression profiles of ACC-M and ACC-2 cell lines makes the foundation for seeking the target genes of adenoid cystic carcinoma. MMP2,MMP7,MMP9 and MMP15 may be relevant with carcinogenesis, development and metastasis of adenoid cystic carcinoma, and different metastasis potential may result from different subtype of MMPs gene family.

Carcinoma, Adenoid Cystic ; enzymology ; genetics ; pathology ; Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Matrix Metalloproteinase 15 ; genetics ; Matrix Metalloproteinase 2 ; genetics ; Matrix Metalloproteinase 7 ; genetics ; Matrix Metalloproteinase 9 ; genetics ; Matrix Metalloproteinases ; genetics ; Neoplasm Metastasis ; Reverse Transcriptase Polymerase Chain Reaction ; methods