OBJECTIVETo measure peripheral serum levels of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 19 (MMP19) in patients with pneumoconiosis, and to investigate their feasibility as potential biomarkers for pneumoconiosis.

METHODSNinety-eight male patients with pneumoconiosis (49 patients in phase I, 36 patients in phase II, and 13 patients in phase III) were enrolled as subjects, which included 41 patients with silicosis and 57 patients with coal workers' pneumoconiosis. Ninety-eight healthy male physical examinees were used as controls. A fasting blood sample (3 ml) was collected from the peripheral venous blood of each patient or control, and the serum was separated from the blood sample. The expression levels of MMP9 and MMP19 in serum were measured by enzyme-linked immunosorbent assay.

RESULTSSerum levels of MMP9 and MMP19 in patients with silicosis or coal workers' pneumoconiosis were significantly lower than those in the control group (P < 0.05). Serum levels of MMP19 in patients with silicosis were significantly higher than those in patients with coal workers' pneumoconiosis (P < 0.05). Serum levels of MMP19 in patients exposed to dust for less than 7 years were significantly higher than those in patients exposed to dust for more than 20 years (P < 0.05). There were no significant differences in serum levels of MMP9 and MMP19 between patients with different levels of pulmonary function impairment (P > 0.05). Serum expression levels of MMP9 and MMP19 were positively correlated with each other in both patients with pneumoconiosis and those in the control group (P < 0.05). The serum expression level of MMP9 was negatively correlated with the stage of pneumoconiosis (P < 0.05).

CONCLUSIONSerum MMP9 and MMP19 may be used as potential biomarkers for pneumoconiosis.

Anthracosis ; enzymology ; Biomarkers ; Coal Mining ; Dust ; Humans ; Lung ; Male ; Matrix Metalloproteinase 9 ; blood ; Matrix Metalloproteinases, Secreted ; blood ; Occupational Exposure ; Pneumoconiosis ; blood ; enzymology ; Silicosis ; enzymology

OBJECTIVETo observe the effect of intra-articular injection of SB203580, a selective p38 mitogen-activated protein kinase inhibitor, on the expression of matrix metalloproteinase (MMP)-3, MMP-13 in a rat model of osteoarthritis (OA) and to explore the relationship between the MMP-3/MMP-13 expressions and the severity of OA.

METHODSFourty SD rats underwent unilateral anterior cruciate ligament transection (ACLT) and then randomly divided into four groups, with 10 rats in each group. Group A received 0.1 ml intra-articular injection of SB203580 at a high concentration of 100 micromol/L (once a week) immediately after surgery, and group B were treated under the same condition using SB203580 with a low concentration of 10 micromol/ L Group C received 0.1 ml intra-articular normal saline, and group D were not injected as controls after ACLT. All rats were sacrificed seven weeks after the surgery. Macroscopic and immunohistochemical studies were performed on the cartilage. Protein expressions of MMP-3 and MMP-13 were determined by Western blot. RESULTS Cartilage degradation was significantly milder in group A and group B than in the control groups, as shown by morphological studies (P < 0. 05) and immunohistochemical studies (P < 0. 05). The protein expressions of MMP-3 and MMP-13 in cartilage were significantly lower in groups A and B than in groups C and D (P < 0.01).

CONCLUSIONSB203580 can inhibit the expressions of MMP-3 and MMP-13 and thus protect the cartilage.

Animals ; Cartilage, Articular ; drug effects ; enzymology ; Imidazoles ; administration & dosage ; pharmacology ; therapeutic use ; Injections, Intra-Articular ; Matrix Metalloproteinase 13 ; metabolism ; Matrix Metalloproteinase 3 ; metabolism ; Matrix Metalloproteinases, Secreted ; metabolism ; Osteoarthritis ; drug therapy ; enzymology ; Protein Kinase Inhibitors ; administration & dosage ; pharmacology ; therapeutic use ; Pyridines ; administration & dosage ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors

The aim of this study was to investigate the expression of matrix metalloproteinase 26 (MMP-26), tissue inhibitor of metalloproteinase-4 (TIMP-4) and matrix metalloproteinase 9 (MMP-9) in patients with diffuse large B cell lymphoma (DLBCL) and their correlations with pathogenesis and development of DLBCL. A total of 95 specimens excised from DLBCL patients were prepared. Expression of MMP-26, TIMP-4 and MMP-9 were tested by SABC immunohistochemistry method and its correlation to clinicopathology indexes were analyzed. The results showed that as compared with reactive hyperplasia of lymph nodes, the high expression of MMP-26, TIMP-4 and MMP-9 were found in different types of DLBCL. The positive expression rate of MMP-26 was related to immune typing (P < 0.05). The expression level of MMP-26 in GCB was lower than that in non-GCB, and did not relate to clinical staging, age, sex, diseased region (P > 0.05). The positive expression rate of MMP-9 was related to clinical staging, the positive expression rate of MMP-9 proteins in patient at III and IV stage was obviously higher than that in patients at I and II stage, but did not relate to immune type, age, sex and diseased region of DLBCL (P > 0.05). The expression of TIMP-4 did not relate to immune type, clinical stage, age, sex, disease region (P > 0.05). The expression of MMP-26 in pathologic tissue of DLBCL did not relate to expression of TIMP-4, but positively related to expression of MMP-9 protein (r = 0.486, P < 0.05). It is concluded that MMP-26 and MMP-9 synergically express in DLBCL. MMP-26 may be involve in pathogenesis and invasiveness of DLBCL, the expression of MMP-26 relates to subtypes of DLBCL. The MMP-26 may serve as an indicator for typing of DLBCL and contributes to predict the invasion and metastasis of DLBCL and itself may become a potential target for therapy.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Matrix Metalloproteinases, Secreted ; metabolism ; Middle Aged ; Tissue Inhibitor of Metalloproteinases ; metabolism ; Young Adult

OBJECTIVEWe investigated the in vivo effects of recombinant adenovirus-associated virus type-2 (AAV-2) mediated interleukin-10 (IL-10) gene transfer on the expression of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of metalloproteinase (TIMP)-1, collagen type I and type III in a rat acute myocardial infarction model.

METHODMale Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 6): sham operation group, MI/AAV2 group, and MI/AAV2-IL-10 group (10(10) vg/ml x 0.1 ml injection at peri-infarct regions immediately post MI). Five days later, the expressions of MMP-2 and MMP-9 were measured by RT-PCR, Western blot and zymography. The expression of TIMP-1 was measured by RT-PCR and Western blot. Collagen type I and type III were assessed by RT-PCR and immunohistochemical stain.

RESULTSThe myocardial expressions of MMP-2, MMP-9 and collagen contents in MI/AAV2 group were significantly increased than those in sham operation group. Myocardial expressions of MMP-2, MMP-9 were significantly decreased and the expression of TIMP-1 significantly increased in the MI/AAV2-IL-10 group than those in MI/AAV2 group. Moreover, the expressions of collagen type I, collagen type III and the ratio of I/III collagen in border zones of infarcted myocardium were decreased by 47.6% (P < 0.01), 23.6% (P < 0.05), and 17.9% (P < 0.05) respectively, while the expression of TIMP-1 increased by 73.1%(P < 0.05) in MI/AAV2-IL-10 group compared to MI/AAV2 group.

CONCLUSIONIn vivo myocardial IL-10 transfer reduced myocardial MMP and collagen expression and increasing the TIMP expression.

Animals ; Extracellular Matrix ; metabolism ; Gene Expression ; Genetic Therapy ; Interleukin-10 ; genetics ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Myocardial Infarction ; genetics ; metabolism ; physiopathology ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Transfection ; Ventricular Remodeling

OBJECTIVE: To investigate the effect of pure Chinese herbal extract Mangiferin on the malignant biological behaviors of multiple myeloma (MM) cells, and to analyze the molecular mechanism of the anti-myeloma effect of Mangiferin, so as to provide experimental basis for MM replacement therapy. METHODS: U266 and RPMI8226 of human MM cell lines were intervened with different concentrations of Mangiferin. Cell proliferation was detected by CCK-8 method. Annexin V/PI double staining flow cytometry was used to detect cell apoptosis. Western blot was used to detect the expression of apoptosis and related signaling pathway proteins, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of matrix metalloproteinase (MMP) and CXC chemokine receptor (CXCR) family. RESULTS: Mangiferin could inhibit the proliferation activity of U266 and RPMI8226 cells and induce cells apoptosis. After Mangiferin intervened in U266, RPMI8226 cells for 48 h, the expression of Bcl-2 family pro-apoptotic protein Bax was up-regulated, while the expression of survivin and Bcl-xL proteins was down-regulated and caspase-3 was hydrolyzed and activated to promote cell apoptosis, besides, the expression of Bcl-2 protein in U266 cells was also significantly down-regulated to induce apoptosis (P<0.05). After Mangiferin intervenes in MM cells, it can not only increase the expression level of tumor suppressor p53, but also induce programmed cell death of MM cells by inhibiting the expression of anti-apoptotic molecules and down-regulating the phosphorylation levels of AKT and NF-κB. In addition, after the intervention of Mangiferin, the expressions of CXCR4, MMP2 and MMP9 in U266 cells were down-regulated (P<0.05), while there is no effect on the expressions of CXCR2, CXCR7 and MMP13 (P>0.05). However, the expressions of CXCR4, MMP9, and MMP13 in RPMI8226 cells were down-regulated (P<0.01), the expression of MMP2 was weakly affected, and the expression of CXCR2 and CXCR7 was basically not affected (P>0.05). CONCLUSION Mangiferin can inhibit the proliferation and induce apoptosis of MM cells, and its mechanism may be related to inhibiting the activation of NF-κB signaling pathway, affecting the expression of Bcl-2 family proteins, and inhibiting the expression of core members of MMP and CXCR family.
Humans ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; Matrix Metalloproteinase 13 ; Cell Line, Tumor ; NF-kappa B ; Multiple Myeloma/pathology* ; Cell Proliferation ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2

BACKGROUNDPressure therapy improves hypertrophic scar healing, but the mechanisms for this process are not well understood. We sought to investigate the differential expression of matrix metalloproteinases (Mmps) and collagen in posttraumatic hypertrophic scar tissue with mechanical pressure and delineate the molecular mechanisms of pressure therapy for hypertrophic scars.

METHODSFibroblast lines of normal skin and scar tissue were established and a mechanical pressure system was devised to simulate pressure therapy. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting assays were used to compare differences in the mRNA and protein expression of Mmps and collagen in scar fibroblasts before and after pressure therapy.

RESULTSThe expression differed between the hypertrophic scar cell line and the normal cell line. RT-PCR assays showed that Collagen I, highly expressed in the hypertrophic scar cell line, decreased significantly after pressure therapy. Mmp2, Mmp9, and Mmp12 expression in the hypertrophic scar tissue increased significantly after pressure therapy (P < 0.05). Western blotting assays further revealed that Mmp9 and Mmp12 expression increased significantly in the hypertrophic scar tissue after pressure therapy (P < 0.05) but not Mmp2 expression (P > 0.05).

CONCLUSIONMechanical pressure induces degradation of Collagen I in hypertrophic scar tissue by affecting the expression of Mmp9 and Mmp12.

Cell Line ; Cicatrix, Hypertrophic ; enzymology ; metabolism ; Collagen Type I ; genetics ; metabolism ; Humans ; Matrix Metalloproteinase 12 ; genetics ; metabolism ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; genetics ; metabolism

OBJECTIVETo compare right atrial structural remodeling and the expression of matrix metalloproteinase (MMP) and tissue inhibitors (TIMP) between patients with unstable angina (UA) and myocardial infarction (MI).

METHODSRight atrial appendages were obtained from 18 patients with UA and 22 patients with MI undergoing coronary artery bypass grafting (CABG) operations. MMP-1, -3, -7, -9 and TIMP-1 protein expressions were detected by immunohistochemistry and RT-PCR. Echocardiography was performed before CABG.

RESULTSThe left and right atrial diameter, left ventricular diameter and mRNA levels of MMP-3, MMP-9 and TIMP-1 were significantly higher in MI group than those in UA group [LAD: (40.8 +/- 4.2) mm vs. (33.1 +/- 5.1) mm, P < 0.01; RAD: (44.1 +/- 6.8) mm vs. (28.8 +/- 6.0) mm, P < 0.01; LVEDD: (48.9 +/- 6.0) mm vs. (39.7 +/- 7.1) mm, P < 0.05; MMP-3: 0.39 +/- 0.18 vs. 0.28 +/- 0.07, P < 0.05; MMP-9: 0.81 +/- 0.21 vs. 0.55 +/- 0.20, P < 0.01; TIMP-1: 1.79 +/- 0.89 vs. 0.94 +/- 0.47, P < 0.01]. MMP-1, MMP-7 levels were similar between the 2 groups (MMP-1: 0.14 +/- 0.06 vs. 0.10 +/- 0.08, P > 0.05; MMP-7: 0.25 +/- 0.05 vs. 0.23 +/- 0.06, P > 0.05).

CONCLUSIONRight atrial up-regulation of MMP-3, MMP-9 and TIMP-1 levels may contribute to the right atrial structural remodeling in MI patients.

Adult ; Aged ; Angina, Unstable ; metabolism ; Female ; Gene Expression Regulation ; Heart Atria ; metabolism ; Humans ; Male ; Matrix Metalloproteinase 1 ; metabolism ; Matrix Metalloproteinase 3 ; metabolism ; Matrix Metalloproteinase 7 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; Myocardial Infarction ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Up-Regulation

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 association between the functional polymorphism of matrix metalloproteinases (MMPs) and the development of chronic obstructive pulmonary disease (COPD).

METHODS147 COPD patients and 120 healthy smoking controls were selected. Spirometry and chest X-rays had been taken. Questionnaires including sex, age, smoking history, occupational exposure were completed. MMP-9 (-1562 C/T), MMP-1(-1607 1G/2G), MMP-12 (-82 A/G), MMP-12(-357 Asn/ Ser) alleles were determined using PCR-RFLP method. Independent samples T test analysis was carried out to compare patients' age, smoking index, FEV1 /FVC, FEV1 % pred with that of healthy controlled group. The frequencies of genotypes and alleles between groups were analyzed by chi-square tests and multilogistic regression.

RESULTSMMP12 Asn/Asn, CT/AsnAsn were risk factors for smoking-induced COPD. The ORs were 2.361 (95% CI: 1.369-4.017) and 2.433(95% CI: 1.159-5.342) respectively while CC/1G1G/ SerSer seemed to be a protective factor for smoking-induced COPD, with OR as 0.457 and 95% CI as 0.231-0.911.

CONCLUSIONAsn/Asn, CT/AsnAsn might be susceptible genotypes while CC/GG/SerSer might serve as protective genotype.

Aged ; Case-Control Studies ; China ; ethnology ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Matrix Metalloproteinase 1 ; genetics ; Matrix Metalloproteinase 12 ; genetics ; Matrix Metalloproteinase 9 ; genetics ; Polymorphism, Genetic ; Pulmonary Disease, Chronic Obstructive ; genetics

Overexpression of HER2 correlates with more aggressive tumors and increased resistance to cancer chemotherapy. However, a functional comparison between the HER2high/HER3 and the HER2low/HER3 dimers on tumor metastasis has not been conducted. Herein we examined the regulation mechanism of heregulin-beta1 (HRG)-induced MMP-1 and -9 expression in breast cancer cell lines. Our results showed that the basal levels of MMP-1 and -9 mRNA and protein expression were increased by HRG treatment. In addition, HRG-induced MMP-1 and -9 expression was significantly decreased by MEK1/2 inhibitor, U0126 but not by phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002. To confirm the role of MEK/ERK pathway on HRG-induced MMP-1 and -9 expression, MCF7 cells were transfected with constitutively active adenoviral-MEK (CA-MEK). The level of MMP-1 and -9 expressions was increased by CA-MEK. MMP-1 and -9 mRNA and protein expressions in response to HRG were higher in HER2 overexpressed cells than in vector alone. The phosphorylation of HER2, HER3, ERK, Akt, and JNK were also significantly increased in HER2 overexpressed MCF7 cells compared with vector alone. HRG-induced MMP-1 and -9 expressions were significantly decreased by lapatinib, which inhibits HER1 and HER2 activity, in both vector alone and HER2 overexpressed MCF7 cells. Finally, HRG-induced MMP-1 and MMP-9 expression was decreased by HER3 siRNA overexpression. Taken together, we suggested that HRG-induced MMP-1 and MMP-9 expression is mediated through HER3 dependent pathway and highly expressed HER2 may be associated with more aggressive metastasis than the low expressed HER2 in breast cancer cells.
Breast Neoplasms/enzymology/*genetics/*metabolism ; Butadienes/pharmacology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MAP Kinase Signaling System ; MCF-7 Cells ; Matrix Metalloproteinase 1/*genetics/metabolism ; Matrix Metalloproteinase 9/*genetics/metabolism ; Neuregulin-1/*pharmacology ; Nitriles/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Multimerization ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/pharmacology ; Receptor, erbB-2/genetics/*metabolism ; Receptor, erbB-3/*metabolism