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Pesquisa : D08.811.277.656.300.480.525.300 [Categoria DeCS]
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[PMID]:28531887
[Au] Autor:Hieronimus B; Pfohl J; Busch C; Graeve L
[Ad] Endereço:Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany.
[Ti] Título:Expression and Characterization of Membrane-Type 4 Matrix Metalloproteinase (MT4-MMP) and its Different Forms in Melanoma.
[So] Source:Cell Physiol Biochem;42(1):198-210, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Membrane-type matrix metalloproteinases (MT-MMPs) are expressed on the cell surface and hydrolyze extracellular matrix components and signaling molecules by which they influence cancer cell migration and metastasis. Two of the six known MT-MMPs are anchored to the plasma membrane via a GPI anchor, one of which is MT4-MMP. Only little is known about MT4-MMP expression, synthesis, regulation and degradation. METHODS: We analyzed several human cancer cell lines as well as tissue homogenates using Western blotting and quantitative PCR for the expression of MT4-MMP. Organelles of SK-Mel-28 cells were separated using continuous Iodixanol gradients. Glycosylation of the SK-Mel-28 protein was studied via glucosidases and site directed mutagenesis of the MT4-MMP cDNA prior to transfection. RESULTS: We found the MT4-MMP highly expressed in human melanoma cell lines as well as skin and melanoma tissue samples. Three forms of MT4-MMP with molecular masses of 45 kDa, 58 kDa and 69 kDa were detected. Further, we demonstrate that the 58 kDa form is the mature protein in the cell membrane, while the 69 kDa form is its precursor found in intracellular compartments. The 69 kDa forms are processed by furin cleavage in the Golgi apparatus. Moreover, we identified Asn318 as the single N-glycosylation site of MT4-MMP. CONCLUSION: We demonstrate the novel expression of MT4-MMP in melanocytic tissues and propose a precursor/product-relationship of the different forms of MT4-MMP in melanoma cells.
[Mh] Termos MeSH primário: Metaloproteinases da Matriz Associadas à Membrana/metabolismo
Melanoma/patologia
Neoplasias Cutâneas/patologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Membrana Celular/metabolismo
Estresse do Retículo Endoplasmático
Glicosilação
Complexo de Golgi/metabolismo
Seres Humanos
Metaloproteinases da Matriz Associadas à Membrana/genética
Melanoma/metabolismo
Mutagênese Sítio-Dirigida
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
RNA Mensageiro/metabolismo
Neoplasias Cutâneas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Isoforms); 0 (RNA, Messenger); EC 3.4.24.- (MMP17 protein, human); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE
[do] DOI:10.1159/000477311


  2 / 960 MEDLINE  
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[PMID]:28196064
[Au] Autor:Yip C; Foidart P; Somja J; Truong A; Lienard M; Feyereisen E; Schroeder H; Gofflot S; Donneau AF; Collignon J; Delvenne P; Sounni NE; Jerusalem G; Noël A
[Ad] Endereço:Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, Liège 4000, Belgium.
[Ti] Título:MT4-MMP and EGFR expression levels are key biomarkers for breast cancer patient response to chemotherapy and erlotinib.
[So] Source:Br J Cancer;116(6):742-751, 2017 Mar 14.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a membrane type matrix metalloproteinase that interacts with epidermal growth factor receptor (EGFR) overexpressed in >50% of TNBC. METHODS: We conducted a retrospective immunohistochemical analysis on human TNBC samples (n=81) and validated our findings in in vitro and in vivo assays. RESULTS: Membrane type-4 matrix metalloproteinase and EGFR are produced in 72.5% of TNBC samples, whereas those proteins are faintly produced by healthy tissues. Unexpectedly, tumour relapse after chemotherapy was reduced in samples highly positive for MT4-MMP. Mechanistically, this is ascribed to a higher sensitivity of MT4-MMP-producing cells to alkylating or intercalating chemotherapeutic agents, as assessed in vitro. In sharp contrast, MT4-MMP expression did not affect tumour cell sensitivity to paclitaxel that interferes with protease trafficking. Importantly, MT4-MMP expression sensitised cancer cells to erlotinib, a tyrosine kinase EGFR inhibitor. In a pre-clinical model, the growth of MT4-MMP overexpressing xenografts, but not of control ones, was reduced by epirubicin or erlotinib. The combination of suboptimal drug doses blocked drastically the growth of MT4-MMP-producing tumours. CONCLUSIONS: We demonstrate that MT4-MMP defines a sub-population of TNBC sensitive to a combination of DNA-targeting chemotherapeutic agents and anti-EGFR drugs.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Biomarcadores Tumorais/metabolismo
Metaloproteinases da Matriz Associadas à Membrana/metabolismo
Recidiva Local de Neoplasia/patologia
Receptor do Fator de Crescimento Epidérmico/metabolismo
Neoplasias de Mama Triplo Negativas/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Epirubicina/administração & dosagem
Cloridrato de Erlotinib/administração & dosagem
Feminino
Seguimentos
Seres Humanos
Técnicas Imunoenzimáticas
Metástase Linfática
Camundongos
Camundongos Nus
Meia-Idade
Recidiva Local de Neoplasia/tratamento farmacológico
Recidiva Local de Neoplasia/metabolismo
Estadiamento de Neoplasias
Prognóstico
Estudos Retrospectivos
Taxa de Sobrevida
Neoplasias de Mama Triplo Negativas/tratamento farmacológico
Neoplasias de Mama Triplo Negativas/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 3Z8479ZZ5X (Epirubicin); DA87705X9K (Erlotinib Hydrochloride); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 3.4.24.- (MMP17 protein, human); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170525
[Lr] Data última revisão:
170525
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170215
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.23


  3 / 960 MEDLINE  
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[PMID]:28121923
[Au] Autor:Wang Y
[Ad] Endereço:Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China.
[Ti] Título:Identifying key stage-specific genes and transcription factors for gastric cancer based on RNA-sequencing data.
[So] Source:Medicine (Baltimore);96(4):e5691, 2017 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: To identify gastric cancer (GC)-associated genes and transcription factors (TFs) using RNA-sequencing (RNA-seq) data of Asians. MATERIALS AND METHODS: The RNA-seq data (GSE36968) were downloaded from Gene Expression Omnibus database, including 6 noncancerous gastric tissue samples, 5 stage I GC samples, 5 stage II GC samples, 8 stage III GC samples, and 6 stage IV GC samples. The gene expression values in each sample were calculated using Cuffdiff. Following, stage-specific genes were identified by 1-way analysis of variance and hierarchical clustering analysis. Upstream TFs were identified using Seqpos. Besides, functional enrichment analysis of stage-specific genes was performed by DAVID. In addition, the underlying protein-protein interactions (PPIs) information among stage IV-specific genes were extracted from STRING database and PPI network was constructed using Cytoscape software. RESULTS: A total of 3576 stage-specific genes were identified, including 813 specifically up-regulated genes in the normal gastric tissues, 2224 stage I and II-specific genes, and 539 stage IV-specific genes. Also, a total of 9 and 11 up-regulated TFs were identified for the stage I and II-specific genes and stage IV-specific genes, respectively. Functional enrichment showed SPARC, MMP17, and COL6A3 were related to extracellular matrix. Notably, 2 regulatory pathways HOXA4-GLI3-RUNX2-FGF2 and HMGA2-PRKCA were obtained from the PPI network for stage IV-specific genes. In the PPI network, TFs HOXA4 and HMGA2 might function via mediating other genes. CONCLUSION: These stage-specific genes and TFs might act in the pathogenesis of GC in Asians.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica/genética
Análise de Sequência de RNA
Neoplasias Gástricas/genética
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Análise por Conglomerados
Colágeno Tipo VI/metabolismo
Proteína HMGA2/metabolismo
Proteínas de Homeodomínio/metabolismo
Seres Humanos
Metaloproteinases da Matriz Associadas à Membrana/metabolismo
Estadiamento de Neoplasias
Osteonectina/metabolismo
Transdução de Sinais/genética
Estômago/metabolismo
Estômago/patologia
Neoplasias Gástricas/patologia
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (COL6A3 protein, human); 0 (Collagen Type VI); 0 (HMGA2 Protein); 0 (Homeodomain Proteins); 0 (Osteonectin); 0 (SPARC protein, human); 0 (Transcription Factors); 127609-92-1 (HOXA4 protein, human); EC 3.4.24.- (MMP17 protein, human); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170224
[Lr] Data última revisão:
170224
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000005691


  4 / 960 MEDLINE  
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[PMID]:27869830
[Au] Autor:Okimoto RA; Breitenbuecher F; Olivas VR; Wu W; Gini B; Hofree M; Asthana S; Hrustanovic G; Flanagan J; Tulpule A; Blakely CM; Haringsma HJ; Simmons AD; Gowen K; Suh J; Miller VA; Ali S; Schuler M; Bivona TG
[Ad] Endereço:Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
[Ti] Título:Inactivation of Capicua drives cancer metastasis.
[So] Source:Nat Genet;49(1):87-96, 2017 Jan.
[Is] ISSN:1546-1718
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metastasis is the leading cause of death in people with lung cancer, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through the development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally regulated transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. Inactivation of CIC relieves repression of its effector ETV4, driving ETV4-mediated upregulation of MMP24, which is necessary and sufficient for metastasis. Loss of CIC, or an increase in levels of its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse outcomes in people with lung and/or gastric cancer. Our findings reveal CIC as a conserved metastasis suppressor, highlighting new anti-metastatic strategies that could potentially improve patient outcomes.
[Mh] Termos MeSH primário: Proteínas E1A de Adenovirus/metabolismo
Carcinoma Pulmonar de Células não Pequenas/secundário
Neoplasias Pulmonares/patologia
Metaloproteinases da Matriz Associadas à Membrana/metabolismo
Proteínas Proto-Oncogênicas/metabolismo
Proteínas Repressoras/antagonistas & inibidores
[Mh] Termos MeSH secundário: Proteínas E1A de Adenovirus/genética
Animais
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/metabolismo
Feminino
Perfilação da Expressão Gênica
Seres Humanos
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/metabolismo
Metaloproteinases da Matriz Associadas à Membrana/genética
Camundongos
Camundongos SCID
Proteínas Proto-Oncogênicas/genética
Proteínas Repressoras/genética
Proteínas Repressoras/metabolismo
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenovirus E1A Proteins); 0 (CIC protein, human); 0 (Cic protein, mouse); 0 (ETV4 protein, human); 0 (Proto-Oncogene Proteins); 0 (Repressor Proteins); EC 3.4.24.- (MMP24 protein, human); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161122
[St] Status:MEDLINE
[do] DOI:10.1038/ng.3728


  5 / 960 MEDLINE  
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[PMID]:27517731
[Au] Autor:Trella KJ; Li J; Stylianou E; Wang VM; Frank JM; Galante J; Sandy JD; Plaas A; Wysocki R
[Ad] Endereço:Department of Orthopedic Surgery, Rush University Medical Center, 1611 W. Harrison Street, Suite 201, Chicago, Illinois, 60612.
[Ti] Título:Genome-wide analysis identifies differential promoter methylation of Leprel2, Foxf1, Mmp25, Igfbp6, and Peg12 in murine tendinopathy.
[So] Source:J Orthop Res;35(5):947-955, 2017 May.
[Is] ISSN:1554-527X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have used a murine Achilles tendinopathy model to investigate whether tissue changes (such as collagen disorganization, chondroid metaplasia, and loss of tensile properties) which are broadly characteristic of human tendinopathies, are accompanied by changes in the expression of chromatin-modifying enzymes and the methylation status of promoter regions of tendon cell DNA. Tendinopathy was induced by two intra-tendinous TGF-ß1 injections followed by cage activity or treadmill running for up to 28 days. Activation of DNA methyltransferases occurred at 3 days after the TGF-ß1 injections and also at 14 days, but only with treadmill activity. Genome-wide Methyl Mini-Seq™ analysis identified 19 genes with differentially methylated promoters, five of which perform functions with an apparent direct relevance to tendinopathy (Leprel2, Foxf1, Mmp25, Igfbp6, and Peg12). The functions of the genes identified included collagen fiber assembly and pericellular interactions, therefore their perturbation could play a role in the characteristic disorganization of fibers in affected tendons. We postulate that a study of the functional genomics of these genes in animal and human tendon could further delineate the pathogenesis of this multi-factorial complex disease. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:947-955, 2017.
[Mh] Termos MeSH primário: Metilação de DNA
Tendinopatia/metabolismo
[Mh] Termos MeSH secundário: Tendão do Calcâneo/patologia
Animais
Proteínas de Transporte/genética
Modelos Animais de Doenças
Fatores de Transcrição Forkhead/genética
Proteínas Ligadas por GPI/genética
Expressão Gênica
Estudo de Associação Genômica Ampla
Masculino
Metaloproteinases da Matriz Associadas à Membrana/genética
Camundongos Endogâmicos C57BL
Proteínas de Neoplasias/genética
Pró-Colágeno-Prolina Dioxigenase/genética
Regiões Promotoras Genéticas
Tendinopatia/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Forkhead Transcription Factors); 0 (Foxf1a protein, mouse); 0 (GPI-Linked Proteins); 0 (Neoplasm Proteins); 0 (Peg12 protein, mouse); EC 1.14.11.2 (Procollagen-Proline Dioxygenase); EC 1.14.11.7 (LEPREL1 protein, mouse); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated); EC 3.4.24.- (matrix metalloproteinase 25)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160813
[St] Status:MEDLINE
[do] DOI:10.1002/jor.23393


  6 / 960 MEDLINE  
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[PMID]:27702483
[Au] Autor:Knapinska AM; Amar S; He Z; Matosevic S; Zylberberg C; Fields GB
[Ad] Endereço:Florida Atlantic University, Department of Chemistry & Biochemistry, Jupiter, FL 33458, United States; Torrey Pines Institute for Molecular Studies, Departments of Chemistry and Biology, Port St. Lucie, FL 34987, United States.
[Ti] Título:Matrix metalloproteinases as reagents for cell isolation.
[So] Source:Enzyme Microb Technol;93-94:29-43, 2016 Nov.
[Is] ISSN:1879-0909
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cell isolation methods for therapeutic purposes have seen little advancement over the years. The original methods of stem cell and islet isolation using bacterial collagenases were developed in the early 1980s and are still used today. Bacterial collagenases are subject to autodegradation, and isolates obtained with these enzymes may be contaminated with endotoxins, reducing cell viability and contributing to toxicity in downstream applications. Here we describe a novel method for isolation of mesenchymal stem cells from adipose tissue (ADSC) utilizing recombinantly produced matrix metalloproteases (MMPs). The ADSCs isolated by MMPs displayed essentially identical morphological and phenotypical characteristics to cells isolated by bacterially-derived collagenase I and Liberase™. Samples isolated with MMPs and Liberase™ had comparable levels of CD73, CD90, and CD105. The adipogenic and osteogenic potential of the ADSCs isolated by MMPs was retained as compared to cells isolated with Liberase™. However, ADSCs isolated by Liberase™ displayed 6% contamination with other cells as per negative markers revealed by PE staining, as opposed to<1% for all MMP-treated samples. MMP-based cell isolation may contribute to optimization of transplantation technology.
[Mh] Termos MeSH primário: Separação Celular/métodos
Metaloproteinases da Matriz
[Mh] Termos MeSH secundário: Adipogenia
Tecido Adiposo/citologia
Diferenciação Celular
Colagenases/metabolismo
Endotoxinas/análise
Ativação Enzimática
Citometria de Fluxo
Proteínas Ligadas por GPI/metabolismo
Seres Humanos
Imunofenotipagem
Indicadores e Reagentes
Metaloproteinase 12 da Matriz/metabolismo
Metaloproteinase 3 da Matriz/metabolismo
Metaloproteinases da Matriz/metabolismo
Metaloproteinases da Matriz Associadas à Membrana/metabolismo
Células Mesenquimais Estromais/citologia
Osteogênese
Proteínas Recombinantes/metabolismo
Termolisina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Endotoxins); 0 (GPI-Linked Proteins); 0 (Indicators and Reagents); 0 (Recombinant Proteins); EC 3.4.24.- (Collagenases); EC 3.4.24.- (Liberase); EC 3.4.24.- (Matrix Metalloproteinases); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated); EC 3.4.24.- (matrix metalloproteinase 25); EC 3.4.24.17 (MMP3 protein, human); EC 3.4.24.17 (Matrix Metalloproteinase 3); EC 3.4.24.27 (Thermolysin); EC 3.4.24.65 (MMP12 protein, human); EC 3.4.24.65 (Matrix Metalloproteinase 12)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161006
[St] Status:MEDLINE


  7 / 960 MEDLINE  
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[PMID]:27349644
[Au] Autor:Baranger K; Khrestchatisky M; Rivera S
[Ad] Endereço:Aix Marseille Univ, CNRS, NICN, Marseille, France.
[Ti] Título:MT5-MMP, just a new APP processing proteinase in Alzheimer's disease?
[So] Source:J Neuroinflammation;13(1):167, 2016 Jun 28.
[Is] ISSN:1742-2094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We have recently identified in a transgenic mouse model of Alzheimer's disease (AD) membrane-type 5-MMP (MT5-MMP) as a new player in Alzheimer's pathogenesis, which displays pro-amyloidogenic features and proteolytic processing of amyloid precursor protein (APP). Another group has reported that MT5-MMP processing of APP may release a novel neurotoxic APP fragment. Although MT5-MMP-mediated APP processing appears to be a key pathogenic step, we hypothesize that MT5-MMP may also contribute to AD pathogenesis through complementary mechanisms that involve the activation of pro-inflammatory pathways and/or APP trafficking.
[Mh] Termos MeSH primário: Doença de Alzheimer/induzido quimicamente
Doença de Alzheimer/genética
Metaloproteinases da Matriz Associadas à Membrana/metabolismo
Metaloproteinases da Matriz Associadas à Membrana/toxicidade
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides/metabolismo
Precursor de Proteína beta-Amiloide/metabolismo
Animais
Citocinas/metabolismo
Modelos Animais de Doenças
Seres Humanos
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Cytokines); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated); EC 3.4.24.- (Mmp24 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160629
[St] Status:MEDLINE
[do] DOI:10.1186/s12974-016-0633-4


  8 / 960 MEDLINE  
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[PMID]:27259858
[Au] Autor:Soria-Valles C; Gutiérrez-Fernández A; Osorio FG; Carrero D; Ferrando AA; Colado E; Fernández-García MS; Bonzon-Kulichenko E; Vázquez J; Fueyo A; López-Otín C
[Ad] Endereço:Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain;
[Ti] Título:MMP-25 Metalloprotease Regulates Innate Immune Response through NF-κB Signaling.
[So] Source:J Immunol;197(1):296-302, 2016 Jul 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Matrix metalloproteases (MMPs) regulate innate immunity acting over proinflammatory cytokines, chemokines, and other immune-related proteins. MMP-25 (membrane-type 6-MMP) is a membrane-bound enzyme predominantly expressed in leukocytes whose biological function has remained largely unknown. We have generated Mmp25-deficient mice to elucidate the in vivo function of this protease. These mutant mice are viable and fertile and do not show any spontaneous phenotype. However, Mmp25-null mice exhibit a defective innate immune response characterized by low sensitivity to bacterial LPS, hypergammaglobulinemia, and reduced secretion of proinflammatory molecules. Moreover, these immune defects can be tracked to a defective NF-κB activation observed in Mmp25-deficient leukocytes. Globally, our findings provide new mechanistic insights into innate immunity through the activity of MMP-25, suggesting that this proteinase could be a potential therapeutic target for immune-related diseases.
[Mh] Termos MeSH primário: Hipergamaglobulinemia/imunologia
Leucócitos/imunologia
Metaloproteinases da Matriz Associadas à Membrana/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Citocinas/metabolismo
Proteínas Ligadas por GPI/genética
Proteínas Ligadas por GPI/metabolismo
Imunidade Inata/genética
Mediadores da Inflamação/metabolismo
Lipopolissacarídeos/imunologia
Metaloproteinases da Matriz Associadas à Membrana/genética
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
NF-kappa B/metabolismo
Ligação Proteica
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (GPI-Linked Proteins); 0 (Inflammation Mediators); 0 (Lipopolysaccharides); 0 (NF-kappa B); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated); EC 3.4.24.- (matrix metalloproteinase 25)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160605
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1600094


  9 / 960 MEDLINE  
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[PMID]:27170199
[Au] Autor:Stalin J; Harhouri K; Hubert L; Garrigue P; Nollet M; Essaadi A; Muller A; Foucault-Bertaud A; Bachelier R; Sabatier F; Pisano P; Peiretti F; Leroyer AS; Guillet B; Bardin N; Dignat-George F; Blot-Chabaud M
[Ad] Endereço:INSERM UMR-S 1076, Aix-Marseille University, UFR Pharmacy, 27 Bd J. Moulin, 13005 Marseille, France.
[Ti] Título:Soluble CD146 boosts therapeutic effect of endothelial progenitors through proteolytic processing of short CD146 isoform.
[So] Source:Cardiovasc Res;111(3):240-51, 2016 Aug 01.
[Is] ISSN:1755-3245
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIMS: Endothelial colony-forming cells (ECFC) constitute an endothelial progenitor fraction with a promising interest for the treatment of ischaemic cardiovascular diseases. As soluble CD146 (sCD146) is a new factor promoting angiogenesis, we examined whether sCD146 priming could improve the therapeutic potential of ECFC and defined the involved mechanism. METHODS AND RESULTS: We investigated the effects of sCD146 priming on regenerative properties of ECFC in vivo. In a mouse model of hindlimb ischaemia, the homing of radiolabelled cells to ischaemic tissue was assessed by SPECT-CT imaging. Soluble CD146 priming did not modify the number of engrafted ECFC but improved their survival capacity, leading to an enhanced revascularization. The mechanism of action of sCD146 on ECFC was studied in vitro. We showed that sCD146 acts in ECFC through a signalosome, located in lipid rafts, containing angiomotin, the short isoform of CD146 (shCD146), VEGFR1, VEGFR2, and presenilin-1. Soluble CD146 induced a sequential proteolytic cleavage of shCD146, with an extracellular shedding followed by an intramembrane cleavage mediated by matrix metalloprotease (MMP)/ADAM and presenilin-1, respectively. The generated intracellular part of shCD146 was directed towards the nucleus where it associated with the transcription factor CSL and modulated the transcription of genes involved in cell survival (FADD, Bcl-xl) and angiogenesis (eNOS). This effect was dependent on both VEGFR1 and VEGFR2, which were rapidly phosphorylated by sCD146. CONCLUSIONS: These findings establish that activation of the proteolytic processing of shCD146, in particular by sCD146, constitutes a promising pathway to improve endothelial progenitors' regenerative properties for the treatment of cardiovascular diseases.
[Mh] Termos MeSH primário: Proteínas ADAM/metabolismo
Células Progenitoras Endoteliais/transplante
Isquemia/cirurgia
Metaloproteinases da Matriz Associadas à Membrana/metabolismo
Músculo Esquelético/irrigação sanguínea
Neovascularização Fisiológica
Regeneração
[Mh] Termos MeSH secundário: Animais
Antígeno CD146/metabolismo
Movimento Celular
Proliferação Celular
Sobrevivência Celular
Células Cultivadas
Modelos Animais de Doenças
Células Progenitoras Endoteliais/enzimologia
Proteína de Domínio de Morte Associada a Fas/genética
Proteína de Domínio de Morte Associada a Fas/metabolismo
Membro Posterior
Isquemia/genética
Isquemia/metabolismo
Isquemia/fisiopatologia
Microdomínios da Membrana/metabolismo
Camundongos
Proteínas Musculares/genética
Proteínas Musculares/metabolismo
Óxido Nítrico Sintase Tipo III/genética
Óxido Nítrico Sintase Tipo III/metabolismo
Fosforilação
Presenilina-1/metabolismo
Isoformas de Proteínas
Proteólise
Transdução de Sinais
Fatores de Tempo
Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
Proteína bcl-X/genética
Proteína bcl-X/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bcl2l1 protein, mouse); 0 (CD146 Antigen); 0 (Fadd protein, mouse); 0 (Fas-Associated Death Domain Protein); 0 (Mcam protein, mouse); 0 (Muscle Proteins); 0 (Presenilin-1); 0 (Protein Isoforms); 0 (Smpx protein, mouse); 0 (bcl-X Protein); 0 (presenilin 1, mouse); EC 1.14.13.39 (Nitric Oxide Synthase Type III); EC 1.14.13.39 (Nos3 protein, mouse); EC 2.7.10.1 (Flt1 protein, mouse); EC 2.7.10.1 (Kdr protein, mouse); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2); EC 3.4.24.- (ADAM Proteins); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160513
[St] Status:MEDLINE
[do] DOI:10.1093/cvr/cvw096


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[PMID]:26974005
[Au] Autor:Schrade A; Kyrönlahti A; Akinrinade O; Pihlajoki M; Fischer S; Rodriguez VM; Otte K; Velagapudi V; Toppari J; Wilson DB; Heikinheimo M
[Ad] Endereço:Children's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Mol
[Ti] Título:GATA4 Regulates Blood-Testis Barrier Function and Lactate Metabolism in Mouse Sertoli Cells.
[So] Source:Endocrinology;157(6):2416-31, 2016 Jun.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Conditional deletion of Gata4 in Sertoli cells (SCs) of adult mice has been shown to increase permeability of the blood-testis barrier (BTB) and disrupt spermatogenesis. To gain insight into the molecular underpinnings of these phenotypic abnormalities, we assessed the impact of Gata4 gene silencing in cell culture models. Microarray hybridization identified genes dysregulated by siRNA-mediated inhibition of Gata4 in TM4 cells, an immortalized mouse SC line. Differentially expressed genes were validated by quantitative RT-PCR analysis of primary cultures of Gata4(flox/flox) mouse SCs that had been subjected to cre-mediated recombination in vitro. Depletion of GATA4 in TM4 cells and primary SCs was associated with altered expression of genes involved in key facets of BTB maintenance, including tight/adherens junction formation (Tjp1, Cldn12, Vcl, Tnc, Csk) and extracellular matrix reorganization (Lamc1, Col4a1, Col4a5, Mmp10, Mmp23, Timp2). Western blotting and immunocytochemistry demonstrated reduced levels of tight junction protein-1, a prototypical tight junction protein, in GATA4-depleted cells. These changes were accompanied by a loss of morphologically recognizable junctional complexes and a decline in epithelial membrane resistance. Furthermore, Gata4 gene silencing was associated with altered expression of Hk1, Gpi1, Pfkp, Pgam1, Gls2, Pdk3, Pkd4, and Ldhb, genes regulating the production of lactate, a key nutrient that SCs provide to developing germ cells. Comprehensive metabolomic profiling demonstrated impaired lactate production in GATA4-deficient SCs. We conclude that GATA4 plays a pivotal role in the regulation of BTB function and lactate metabolism in mouse SCs.
[Mh] Termos MeSH primário: Fator de Transcrição GATA4/metabolismo
Lactatos/metabolismo
Células de Sertoli/metabolismo
Testículo/metabolismo
[Mh] Termos MeSH secundário: Animais
Barreira Hematotesticular/metabolismo
Western Blotting
Colágeno Tipo IV/metabolismo
Fator de Transcrição GATA4/genética
Imuno-Histoquímica
Laminina/metabolismo
Masculino
Metaloproteinase 10 da Matriz/metabolismo
Metaloproteinases da Matriz Associadas à Membrana/metabolismo
Camundongos
RNA Interferente Pequeno
Espermatogênese/fisiologia
Junções Íntimas/metabolismo
Proteína da Zônula de Oclusão-1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Col4a1 protein, mouse); 0 (Col4a5 protein, mouse); 0 (Collagen Type IV); 0 (GATA4 Transcription Factor); 0 (Gata4 protein, mouse); 0 (Lactates); 0 (Laminin); 0 (RNA, Small Interfering); 0 (Tjp1 protein, mouse); 0 (Zonula Occludens-1 Protein); 0 (laminin gamma 1); EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated); EC 3.4.24.- (Mmp24 protein, mouse); EC 3.4.24.22 (Matrix Metalloproteinase 10)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160315
[St] Status:MEDLINE
[do] DOI:10.1210/en.2015-1927



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