Extracellular Matrix Metalloproteinase Inducer Protein Research Articles

Expression profiles of MMP-9 and EMMPRIN in chronic rhinosinusitis with nasal polyps.

Metalloproteinases (MMPs) are implicated in tissue remodeling in chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the expression profiles of MMP-9 and the extracellular matrix metalloproteinase inducer (EMMPRIN) in nasal polyps compared to healthy mucosa. Tissue samples from 37 CRSwNP patients undergoing functional endoscopic sinus surgery and mucosal specimens from 12 healthy controls were obtained intra-operatively. MMP-9 and EMMPRIN mRNA levels were assessed by reverse transcription-polymerase chain reaction and their protein expression by Western blot analysis. MMP-9 mRNA expression levels were significantly elevated in CRSwNP compared to controls (p < 0.05). MMP-9 protein levels presented an increasing trend but with no statistical significance (p > 0.05). No statistically significant difference in EMMPRIN mRNA and protein levels was identified. Upregulation of MMP-9 in nasal polyps is evident and highlights its role in the pathogenesis of CRSwNP. The lack of concordance between MMP-9 mRNA and protein levels may be attributed to post-translational gene expression regulation. Although EMMPRIN expression was not significantly different between the two groups, its role remains to be elucidated. MMP-9 may be a valuable biomarker and treatment target in CRSwNP.

S-nitrosylation of EMMPRIN influences the migration of HSCs and MMP activity in liver fibrosis.

The mechanism of extracellular matrix metalloproteinase inducer (EMMPRIN) in the regulation of liver fibrosis has not been clarified. This study aims to investigate the role of EMMPRIN S-nitrosylation (SNO) in the regulation of hepatic stellate cell (HSC) migration and matrix metalloproteinase (MMP) activities in liver fibrosis. The results from the tissue microarrays and rat/mouse liver tissues suggest that EMMPRIN mRNA and protein levels in the fibrotic livers are lower than those in the corresponding normal control livers, but higher SNO level of EMMPRIN in fibrotic liver area was shown by immunohistochemistry, immunofluorescence staining, and biotin-switch assay conversely in vivo. Primary EMMPRIN comes from hepatocytes and liver sinus epithelial cells (LSECs) rather than quiescent HSCs. To mimic the uptake of extrinsic EMMPRIN, supernatants from mouse primary hepatocytes/293 cells transfected with EMMPRIN wild-type plasmids (WT) and EMMPRIN SNO site (cysteine 87) mutation plasmids (MUT) were collected and added to JS-1/LX2 cell medium. The MUT EMMPRIN diminishes SNO successfully, enhances the activities of MMP2 and MMP9, and subsequently increases HSC migration. In conclusion, SNO of EMMPRIN influences HSC migration and MMP activities in liver fibrosis. This finding may shed light on the possible regulatory mechanism of MMPs in ECM accumulation in liver fibrosis.

La ivabradina induce cardioprotección previniendo la degradación de la matriz extracelular inducida por shock cardiogénico

Introduction and objectivesIvabradine reduces heart rate by blocking the I(f) current and preserves blood pressure and stroke volume through unknown mechanisms. Caveolin-3 protects the heart by forming protein complexes with several proteins, including extracellular matrix (ECM)-metalloproteinase-inducer (EMMPRIN) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HN4), a target of ivabradine. We hypothesized that ivabradine might also exert cardioprotective effects through inhibition of ECM degradation. MethodsIn a porcine model of cardiogenic shock, we studied the effects of ivabradine on heart integrity, the levels of MMP-9 and EMMPRIN, and the stability of caveolin-3/HCN4 protein complexes with EMMPRIN. ResultsAdministration of 0.3 mg/kg ivabradine significantly reduced cardiogenic shock-induced ventricular necrosis and expression of MMP-9 without affecting EMMPRIN mRNA, protein, or protein glycosylation (required for MMP activation). However, ivabradine increased the levels of the caveolin-3/LG-EMMPRIN (low-glycosylated EMMPRIN) and caveolin-3/HCN4 protein complexes and decreased that of a new complex between HCN4 and high-glycosylated EMMPRIN formed in response to cardiogenic shock. We next tested whether caveolin-3 can bind to HCN4 and EMMPRIN and found that the HCN4/EMMPRIN complex was preserved when we silenced caveolin-3 expression, indicating a direct interaction between these 2 proteins. Similarly, EMMPRIN-silenced cells showed a significant reduction in the binding of caveolin-3/HCN4, which regulates the I(f) current, suggesting that, rather than a direct interaction, both proteins bind to EMMPRIN. ConclusionsIn addition to inhibition of the I(f) current, ivabradine may induce cardiac protection by inhibiting ECM degradation through preservation of the caveolin-3/LG-EMMPRIN complex and control heart rate by stabilizing the caveolin-3/HCN4 complex.

Ivabradine induces cardiac protection by preventing cardiogenic shock-induced extracellular matrix degradation

Introduction and objectivesIvabradine reduces heart rate by blocking the I(f) current and preserves blood pressure and stroke volume through unknown mechanisms. Caveolin-3 protects the heart by forming protein complexes with several proteins, including extracellular matrix (ECM)-metalloproteinase-inducer (EMMPRIN) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HN4), a target of ivabradine. We hypothesized that ivabradine might also exert cardioprotective effects through inhibition of ECM degradation. MethodsIn a porcine model of cardiogenic shock, we studied the effects of ivabradine on heart integrity, the levels of MMP-9 and EMMPRIN, and the stability of caveolin-3/HCN4 protein complexes with EMMPRIN. ResultsAdministration of 0.3 mg/kg ivabradine significantly reduced cardiogenic shock-induced ventricular necrosis and expression of MMP-9 without affecting EMMPRIN mRNA, protein, or protein glycosylation (required for MMP activation). However, ivabradine increased the levels of the caveolin-3/LG-EMMPRIN (low-glycosylated EMMPRIN) and caveolin-3/HCN4 protein complexes and decreased that of a new complex between HCN4 and high-glycosylated EMMPRIN formed in response to cardiogenic shock. We next tested whether caveolin-3 can bind to HCN4 and EMMPRIN and found that the HCN4/EMMPRIN complex was preserved when we silenced caveolin-3 expression, indicating a direct interaction between these 2 proteins. Similarly, EMMPRIN-silenced cells showed a significant reduction in the binding of caveolin-3/HCN4, which regulates the I(f) current, suggesting that, rather than a direct interaction, both proteins bind to EMMPRIN. ConclusionsIn addition to inhibition of the I(f) current, ivabradine may induce cardiac protection by inhibiting ECM degradation through preservation of the caveolin-3/LG-EMMPRIN complex and control heart rate by stabilizing the caveolin-3/HCN4 complex.

Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross-sectional study.

It has been reported that EMMPRIN is involved in the regulation of immune response and the induction of MMPs production by fibroblasts. The aim of this study was to describe the intestinal gene expression and protein production of EMMPRIN, MMP23 and MMP10 in patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared them with a control group. Gene expression of EMMPRIN, MMP10 and MMP23B was measured by RT-PCR. In order to determine EMMPRIN and MMP protein expression, colonic tissues were immunostained. The results of the study showed EMMPRIN gene expression was upregulated in rectal mucosa from active (a)UC versus aCD patients (P=.045), remission (r)CD group (P=.0009) and controls (P<.0001). We detected differences between rUC and aCD (P=.004), rCD (P<.0001) or control group (P<.0001). EMMPRIN showed a higher expression in mucosa (intraepithelial lymphocytes), submucosa and adventitia (endothelial cells) from aCD patients. MMP23 levels were increased in aUC and aCD compared to rUC and rCD and the control group (P=.0001). EMMPRIN+/MMP23+─expressing cells were localized mainly in mucosa, muscular and adventitia from active UC patients. MMP10 gene expression was increased in aUC versus CD patients and the control group (P=.0001). MMP10 gene expression is associated with inflammation in UC patients (P=.0001, r2 =.585). EMMPRIN+/MMP10+─producing cells were found mainly in all intestinal layers and perivascular inflammatory infiltrates from aUC patients. In conclusion, EMMPRIN, MMP23 and MMP10 were upregulated in patients with active UC versus remission UC , CD and control groups suggesting that, they are involved in the inflammatory process.

Expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and -9 in horses with chronic airway inflammation.

OBJECTIVE To examine whether expression of extracellular matrix metalloproteinase inducer (EMMPRIN) can be detected in equine lungs and whether it correlates with matrix metalloproteinase (MMP)-2 and -9 expression in bronchoalveolar lavage fluid (BALF) of horses with chronic inflammation of the lungs (ie, lower airway inflammation [LAI]). ANIMALS 29 horses with signs of chronic respiratory tract disease, which were classified as the LAI (n = 17) and LAI with respiratory distress (RDLAI [12]) groups, and 15 control horses. PROCEDURES BALF, tracheal aspirate, and blood samples were obtained, and EMMPRIN expression was determined from BALF cells and RBCs by use of western blotting. Activities of MMP-2 and -9 were determined with zymography. RESULTS Expression of EMMPRIN protein was identified in BALF cells of all horses. Expression of EMMPRIN protein was highest for the RDLAI group and was correlated with MMP-2 and -9 protein expression, MMP-9 gelatinolytic activity, and airway neutrophilia. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that EMMPRIN was involved in the pathophysiologic processes of asthma in horses. However, additional studies of horses and other species are warranted to elucidate the regulation of EMMPRIN expression in asthmatic lungs.

Spatiotemporal expression of caveolin-1 and EMMPRIN during mouse tooth development.

Caveolin-1 is a scaffolding protein involved in the formation of cholesterol-rich caveolae lipid rafts within the plasma membrane and is capable of collecting signaling molecules into the caveolae and regulating their activity, including extracellular matrix metalloproteinase inducer (EMMPRIN). However, detailed expression patterns of caveolin-1 and EMMPRIN in the developing dental germ are largely unknown. The present study investigated the expression patterns of caveolin-1 and EMMPRIN in the developing mouse tooth germ by immunohistochemistry and real-time polymerase chain reaction. At the bud stage, caveolin-1 expression was initiated in the epithelium bud and mesenchymal cells, while EMMPRIN was weakly expressed at this stage. At the cap stage, caveolin-1 protein was located in the lingual part of the tooth germ; however, EMMPRIN protein was located in the labial part. From the bell stage to 2days postnatal, caveolin-1 expression was detected in the ameloblasts and cervical loop area; with EMMPRIN expression in the ameloblasts and odontoblasts. Real-time polymerase chain reaction results showed that both caveolin-1 and EMMPRIN mRNA levels increased gradually with progression of developmental stages, and peaked at day two postnatal. The current finding suggests that both caveolin-1 and EMMPRIN take part in mouse tooth development, especially in the differentiation and organization of odontogenic tissues.

Homocysteine elicits an M1 phenotype in murine macrophages through an EMMPRIN-mediated pathway.

Hyperhomocysteinemia (HHcy) is associated with inflammatory diseases and is known to increase the production of reactive oxygen species (ROS), matrix metalloproteinase (MMP)-9, and inducible nitric oxide synthase, and to decrease endothelial nitric oxide production. However, the impact of HHcy on macrophage phenotype differentiation is not well-established. It has been documented that macrophages have 2 distinct phenotypes: the "classically activated/destructive" (M1), and the "alternatively activated/constructive" (M2) subtypes. We hypothesize that HHcy increases M1 macrophage differentiation through extracellular matrix metalloproteinase inducer (EMMPRIN), a known inducer of matrix metalloproteinases. murine J774A.1 and Raw 264.7 macrophages were treated with 100 and 500 μmol/L Hcy, respectively, for 24 h. Samples were analyzed using Western blotting and immunocytochemistry. Homocysteine treatment increased cluster of differentiation 40 (CD40; M1 marker) in J774A.1 and Raw 264.7 macrophages. MMP-9 was induced in both cell lines. EMMPRIN protein expression was also increased in both cell lines. Blocking EMMPRIN function by pre-treating cells with anti-EMMPRIN antibody, with or without Hcy, resulted in significantly lower expression of CD40 in both cell lines by comparison with the controls. A DCFDA assay demonstrated increased ROS production in both cell lines with Hcy treatment when compared with the controls. Our results suggest that HHcy results in an increase of the M1 macrophage phenotype. This effect seems to be at least partially mediated by EMMPRIN induction.

ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.

The role of EMMPRIN expression in ovarian epithelial carcinomas

Purpose: Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas. Methods: EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemisty. Results: EMMPRIN siRNA treatment resulted in a lower growth, G1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (P < 0.05), and positively correlated with dedifferentiation and FIGO staging (P < 0.05). Immuhistochemically, EMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (P < 0.05). Conclusions: Upregulated expression of EMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion.

OP052: EMMPRIN expression in oral squamous cell carcinomas

Purposes Our aim was to evaluate the expression of the extracellular matrix metalloproteinase inducer (EMMPRIN) in oral squamous cell carcinomas (OSCC). We examined their utility as prognostic marker by relating to clinicopathological characteristics and the clinical outcome. Materials and methods Using tissue microarray technology we analysed 77 primary OSCC and examined immunohistochemical expression of EMMPRIN protein. Multivariate analysis was conducted to examine their role in survival. Results EMMPRIN overexpression was observed in 56 cases (72.7%) with both membrane and cytoplasmic expression in 49 (63.6%). No significant relationships were found between clinicopathologic factors and this protein except for histological grade. Moderate or poorly differentiated tumours showed overexpression of this protein more frequently then well differentiated tumours ( p = 0.002). In univariate analysis, T stage ( p p = 0.001), tumour stage ( p p = 0.017), and EMMPRIN expression ( p = 0.011), were statistically correlated to overall survival (OS). The same was observed with reference to disease-free survival (DFS) for gender ( p = 0.006), T stage ( p = 0.003), N status ( p = 0.002), tumour stage ( p = 0.003), and surgical margins ( p = 0.004). In the multivariate analysis for OS we found an adverse independent prognostic value for EMMPRIN overexpression ( p = 0.007) and for advanced tumour stage ( p = 0.001). For DFS, only advanced tumour stage ( p = 0.004), presented adverse independent prognostic value. Conclusion EMMPRIN protein is overexpressed in more than two thirds of the cases of OSCC and is an indicator of lower overall survival for these patients. The independent value of EMMPRIN overexpression in overall survival of OSCC suggests that this marker may serve as reliable biological marker to identify high-risk subgroups and to guide therapy. Moreover the high expression of this marker could be regarded as potential therapeutic target in OSCC.

Decreased Tissue Levels of Cyclophilin A, a Cyclosporine A Target and Phospho-ERK1/2 in Simvastatin Patients with Abdominal Aortic Aneurysm

Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in animal and in vitro studies. Statins decrease CyPA in smooth muscle cells although their influence on CyPA in human AAA is unknown. The study was performed on AAA wall-tissue samples obtained from 30 simvastatin-treated and 15 non-statin patients (2:1 case to control). The patients were matched by age, sex and AAA diameter. We investigated the gene expression of CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot. The AAA wall tissue from simvastatin-treated patients had significantly lower CyPA gene expression and protein levels (P = 0.0018, P = 0.0083, respectively). Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the simvastatin group (P = 0.0002, P = 0.0027, respectively). However, simvastatin did not influence EMMPRIN gene and protein expression. Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the interference with signalling pathways leading to CyPA formation and ERK1/2 activation reveals a new anti-inflammatory role of statins in AAA.

EMMPRIN Is an Independent Negative Prognostic Factor for Patients with Astrocytic Glioma

Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). It has been proved to be associated with tumor invasion and metastasis in various human malignancies. In our study, the protein expression level of EMMPRIN in 306 cases of astrocytic glioma is investigated by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of EMMPRIN with clinicopathological characteristics and prognosis of patients. It was proved that EMMPRIN protein expression was increased in glioma compared with that in normal brain tissue. Moreover, EMMPRIN immunohistochemical staining was correlated with WHO grade and Karnofsky performance score for strong positive EMMPRIN staining is more frequently detected in glioma of advanced grade or low KPS score. It is also demonstrated that EMMPRIN could be an independent negative prognostic factor in glioma for patients with glioma of strong EMMPRIN staining tend to have high risk of death. These results proved that EMMPRIN is associated with prognosis of glioma, which may also suggest the potential role of EMMPRIN in glioma management.

EMMPRIN Is Secreted by Human Uterine Epithelial Cells in Microvesicles and Stimulates Metalloproteinase Production by Human Uterine Fibroblast Cells

Endometrial remodeling is a physiological process involved in the gynecological disease, endometriosis. Tissue remodeling is directed by uterine fibroblast production of matrix metalloproteinases (MMPs). Several MMPs are regulated directly by the protein extracellular matrix metalloproteinase inducer (EMMPRIN) and also by proinflammatory cytokines such as interleukin (IL)1-α/β. We hypothesized that human uterine epithelial cells (HESs) secrete intact EMMPRIN to stimulate MMPs. Microvesicles from HES cell-conditioned medium (CM) expressed intact EMMPRIN protein. Treatment of HES cells with estradiol or phorbyl 12-myristate-13-acetate increased the release of EMMPRIN-containing microvesicles. The HES CM stimulated MMP-1, -2, and -3 messenger RNA levels in human uterine fibroblasts (HUFs) and EMMPRIN immunodepletion from HES-cell concentrated CM reduced MMP stimulation (P < .05). Treatment of HUF cells with low concentrations of IL-1β/α stimulated MMP production (P < .05). These results indicate that HES cells regulate MMP production by HUF cells by secretion of EMMPRIN, in response to ovarian hormones, proinflammatory cytokines as well as activation of protein kinase C.

Temporal expression of metalloproteinase‐8 and ‐13 and their relationships with extracellular matrix metalloproteinase inducer in the development of ligature‐induced periodontitis in rats

Matrix metalloproteinases (MMPs) play important roles in extracellular matrix degradation and may be regulated by extracellular matrix metalloproteinase inducer (EMMPRIN). The aim of this study was to investigate the temporal expression and localization of MMP-8 and MMP-13 during the development of ligature-induced periodontitis in rats, and to analyze the correlations of EMMPRIN with MMP-8 and MMP-13 in periodontitis. Periodontitis was simulated in rats by ligaturing the cervix of the lower first molars, as described in our previous method. The rats were killed 0, 3, 5, 7, 11, 15 and 21 d after ligation. Micro-computed tomography examinations were performed to detect alveolar bone loss. Semiquantitative western blotting was used to assess the temporal changes in the levels of MMP-8, MMP-13 and EMMPRIN proteins in gingival tissue. Immunohistochemistry was applied to detect the expression and locations of MMP-8 and MMP-13 in gingival tissue and alveolar bone. Alveolar bone loss showed an exponential increase from days 3 to 11, followed by a slower rate of loss at subsequent study time points. MMP-8 showed a rapid increase of expression from baseline to a peak on day 3, a gradual decrease from days 5 to 7 and then stabilized thereafter. MMP-8 was predominantly located in neutrophil-like cells. Statistically, the expression of MMP-8 was not correlated with the expression of EMMPRIN. The expression of MMP-13 and of EMMRPIN increased from days 3 to 7, and showed a moderate decrease thereafter. The immunoreactivity of MMP-13 was mainly detected in monocytes/macrophages, on the alveolar bone surface, in osteoclasts and in gingival epithelial cells. Statistically, MMP-13 had a strong, positive correlation with EMMPRIN (r = 0.855, p < 0.01). The levels of expression of MMP-8 and MMP-13 are temporally varied at different periods during the development of experimental periodontitis. The level of expression of EMMPRIN is closely associated with the expression of MMP-13, but not with the expression of MMP-8. In addition, MMP-13 might be involved in alveolar bone destruction, as well as in physiological bone remodeling.

Extracellular Matrix Metalloproteinase Inducer is Associated with Severity of Brain Oedema following Experimental Subarachnoid Haemorrhage in Rats

Brain oedema is a major cause of clinical deterioration and death following brain trauma; cellular mechanisms involved in its development remain elusive. This study investigated the role of extracellular matrix metalloproteinase inducer (EMMPRIN) in brain oedema. The monofilament puncture model was used to induce subarachnoid haemorrhage. Adult male Sprague-Dawley rats were divided into five groups (n = 20 per group): sham-operated, sacrificed immediately after surgery (sham group); sacrificed 12, 24 or 72 h after subarachnoid haemorrhage induction (SAH-12, SAH-24 and SAH-72 groups, respectively); treated with EMMPRIN inhibitor immediately after subarachnoid haemorrhage, sacrificed at 24 h (SAH-inhibition group). Mean brain water content, and EMMPRIN mRNA and protein levels, were determined. Compared with the sham group, mean brain water content, EMMPRIN mRNA and protein levels in the SAH-12, SAH-24 and SAH-72 groups increased rapidly and significantly (maximal at 24 h). EMMPRIN inhibition significantly reduced mean brain water content and EMMPRIN mRNA and protein levels in the SAH-inhibition group, compared with the SAH-24 group. EMMPRIN upregulation may be important in the formation of brain oedema; inhibition of EMMPRIN activity may provide a potential approach to reduce oedema after subarachnoid haemorrhage.

High extracellular matrix metalloproteinase inducer/CD147 expression is strongly and independently associated with poor prognosis in colorectal cancer

As in most solid tumors, colorectal cancer prognosis strongly depends on the extent of local invasion and lymph node and distant metastases. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that activates matrix metalloproteinases, a group of enzymes that play an important role in tumor invasion and metastasis formation. This study investigates the EMMPRIN expression in a large cohort of patients with colorectal cancer. Immunohistochemical analysis of tissue microarrays from 285 patients shows that increased EMMPRIN protein expression does not correlate with clinicopathologic parameters and is an independent prognostic factor of poor survival, with mean survival times of 103 months in EMMPRIN negative/low versus 57 months in EMMPRIN intermediate/high patients (P < .001). This pronounced association of increased EMMPRIN levels and--on average--a 45% reduction in overall survival could help improve the risk stratification in patients with colorectal cancer; moreover, the lack of correlations with classical measures of cancer invasion/spreading may suggest the relevance of alternative EMMPRIN pathways beyond matrix metalloproteinase activation.

Over-expression of extracellular matrix metalloproteinase inducer in prostate cancer is associated with high risk of prostate-specific antigen relapse after radical prostatectomy

The prognostic efficiency of clinical grading and staging in patients with confined or moderately differentiated prostate cancer (PCa) has been markedly improved, which underscores the importance of new prognostic markers. Extracellular matrix metalloproteinase inducer (EMMPRIN) has been demonstrated to be involved in cancerangiogenesis, metastasis and invasion. EMMPRIN expression was evaluated by measuring mRNA and protein levels in a large cohort of patients with PCa following prostatectomy and the findings were compared with clinico-pathological parameters, including prostate-specific antigen (PSA) relapse time. EMMPRIN mRNA levels in 20 pairs of normal and cancerous prostate tissues were determined by quantitative real-time PCR. Protein expression in paraffin-embedded specimens of prostates gathered from 300 patients with PCa was detected by immunohistochemistry using a monoclonal antibody against EMMPRIN. The associations of EMMPRIN protein expression with the clinico-pathological parameters and PSA relapse-free time after radical prostatectomy were subsequently assessed. Both EMMPRIN mRNA and protein levels were higher in PCa tissue, compared with adjacent normal tissue. In addition, the positive expression rates of EMMPRIN in PCa tissues were significantly associated with preoperative PSA levels (p=0.008), AJCC stage (p=0.006) and Gleason Score (p < 0.001), Risk classification (p < 0.001), lymph node status post-surgery (p < 0.001) and surgical margin status (p < 0.001) were also determined. Multivariate analysis, using the Cox proportional hazards model, revealed that positive EMMPRIN expression was an independent prognostic factor for an increased risk of PSA relapse. Over-expression of EMMPRIN correlated with the aggressiveness of PCa, and the PSA relapse-free time, and may be a novel and useful biomarker for follow-up and treatment decisions for PCa.

Angiotensin II induces extracellular matrix metalloproteinase inducer expression via an AT1R dependent pathway in aortic atherosclerotic plaque in apolipoprotein E knockout mice

The pathogenesis of acute coronary syndrome is rupture of vulnerable plaque. Extracellular matrix metalloproteinase inducer (EMMPRIN) is reported to have a important role in the destabilization of atheroma. this investigation examined the effect of angiotensin II (Ang II) on EMMPRIN expression in atherosclerotic plaques in ApoE knockout mice. ApoE knockout mice were fed a high fat diet to establish an atherosclerosis model then intervention was made with Ang II and valsartan. EMMPRIN gene and its protein expression were measured by real-time PCR immunohistochemistry, and Western blot. EMMPRIN gene and protein expression intervened with Ang II were significantly increased; valsartan could inhibit the effect of Ang II. Ang II up-regulated EMMPRIN expression in atherosclerotic plaque via AT1R, and valsartan could inhibit the effect of Ang II.

Clinicopathologic significance of fascin, extracellular matrix metalloproteinase inducer, and ezrin expressions in colorectal adenocarcinoma

The over expression of fascin, extracellular matrix metalloproteinase inducer (EMMPRIN), and ezrin proteins has been associated with poor prognosis in various carcinomas and sarcomas. However, very few studies have reported the relationship between the expression of fascin, EMMPRIN, and ezrin proteins and the clinico-pathologic parameters of colorectal carcinomas. The aim was to investigate the relationship between fascin, EMMPRIN, and ezrin proteins in colorectal adenocarcinomas and their correlation with clinico-pathologic parameters. The expression of fascin, EMMPRIN, and ezrin proteins was studied in 210 colorectal adenocarcinoma patients through immunohistochemical staining. Immunohistochemical staining by the avidin-biotin peroxidase method was done. The scoring of each protein expression was done and divided into three groups (negative, low-, and high-expression groups). A chi-square test, and Kendall's tau-b correlation test were used for comparing. Survival analysis was performed using the Kaplan-Meier method with log-rank tests and the Cox proportional hazard model. The percentages of the high-expression group of fascin, EMMPRIN, and ezrin proteins in colorectal adenocarcinomas were 24%, 73%, and 62%, respectively. Weak positive correlations were observed among these protein expressions. An increased expression of the fascin protein was significantly associated with advanced tumor depth and shorter survival times, and a high expression of fascin protein was an independent prognostic factor in univariate and multivariate survival analyses. EMMPRIN and ezrin protein expressions were not associated with the clinico-pathologic parameters. The high expression of fascin protein may be an unfavorable prognostic marker for individual colorectal cancer patients.