ABSTRACT
Double-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of miRNA-21, PELI1, and SPRY2. There are two ADAR1 isoforms in humans, ADAR1-p110 and ADAR1-p150, generated by an alternative promoter. Let-7d is considered an essential microRNA in Pulmonary Fibrosis (PF). In silico analysis revealed COL3A1 and SMAD2, proteins involved in the development of IPF, as Let-7d targets. We analyzed the role of ADAR1-p110 and ADAR1-p150 isoforms in the regulation of Let-7d maturation and the effect of this regulation on the expression of COL3A1 and SMAD2 in IPF fibroblast. We demonstrated that differential expression and subcellular distribution of ADAR1 isoforms in fibroblasts contribute to the up-regulation of pri-miR-Let-7d and down-regulation of mature Let-7d. Induction of overexpression of ADAR1 reestablishes the expression of pri-miR-Let-7d and Let-7d in lung fibroblasts. The reduction of mature Let-7d upregulates the expression of COL3A1 and SMAD2. Thus, ADAR1 isoforms and Let-7d could have a synergistic role in IPF, which is a promising explanation in the mechanisms of fibrosis development, and the regulation of both molecules could be used as a therapeutic approach in IPF.
Subject(s)
Adenosine Deaminase , Idiopathic Pulmonary Fibrosis , MicroRNAs , Adenosine Deaminase/genetics , Adenosine Deaminase/metabolism , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Lung/metabolism , Membrane Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA-Binding ProteinsABSTRACT
BACKGROUND: The C allele of c.-94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). AIM: We evaluated whether the c.-94C>G polymorphism can be a risk factor for HCM in Mexican patients. METHODS: The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. RESULTS: The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. CONCLUSIONS: The C allele of the c.-94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients.
Subject(s)
Cardiomyopathy, Hypertrophic/genetics , Genetic Predisposition to Disease , Sarcoglycans/genetics , Adult , Case-Control Studies , Female , Humans , Male , Mexico , Middle Aged , Mutation , Risk FactorsABSTRACT
This study evaluates the prognostic value of MAGE-A3 expression in 28 diffuse large B-cell lymphoma (DLBCL) patients. A significant association was observed between MAGE-A3 expressions, assessed by quantitative real-time RT-polymerase chain reaction (PCR), with advanced stages of disease (P < 0.05). Elevated serum lactate dehydrogenase (LDH) levels and International Prognostic Index (IPI) score were significantly higher in MAGE-A3-positive patients (P = 0.025 and P = 0.004, respectively). Expression of MAGE-A3 was associated with poor response to treatment and a significantly shorter overall survival (P < 0.001). Our data address new information in the association of MAGE-A3 expression and poor prognosis in DLBCL patients.
Subject(s)
Antigens, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Lymphoma, Large B-Cell, Diffuse/genetics , Neoplasm Proteins/genetics , Adolescent , Adult , Aged , Antigens, Neoplasm/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blotting, Western , Female , Humans , L-Lactate Dehydrogenase/blood , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/metabolism , Male , Middle Aged , Neoplasm Proteins/metabolism , Neoplasm Staging , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Survival Analysis , Time Factors , Treatment Outcome , Young AdultABSTRACT
Endothelial cells are susceptible to infection by several pathogens, but little is known about mycobacterial infection. We analyzed some features of mycobacteria-endothelial cell interactions and the innate response to the infection. Intracellular growth in human umbilical vein endothelial cells (HUVECs) of three Mycobacterium species: M. tuberculosis (MTB), M. abscessus (MAB) and M. smegmatis (MSM) was analyzed. M. smegmatis was eliminated; M. abscessus had an accelerate intracellular replication and M. tuberculosis did not replicate or was eliminated. M. abscessus infection induced profound cytoskeleton rearrangements, with M. tuberculosis infection changes were less marked, and with MSM were slight. Nitric oxide (NO) production was induced differentially: M. abscessus induced the highest levels followed by M. tuberculosis and M. smegmatis; the contrary was true for reactive oxygen species (ROS) production. Only M. tuberculosis infection caused beta-1 defensin over-expression. As a whole, our results describe some aspects of the innate response of HUVEC infected by mycobacteria with different virulence and suggest that a strong cytoskeleton mobilization triggers a high NO production in these cells.
Subject(s)
Defensins/biosynthesis , Endothelial Cells/immunology , Endothelial Cells/microbiology , Immunity, Innate , Mycobacterium Infections/immunology , Mycobacterium smegmatis/growth & development , Bacterial Load , Cytoskeleton/ultrastructure , Defensins/analysis , Endothelial Cells/cytology , Endothelial Cells/ultrastructure , Female , Fetus , Host-Parasite Interactions , Humans , Microscopy, Electron, Scanning , Mycobacterium/growth & development , Mycobacterium/pathogenicity , Mycobacterium Infections/microbiology , Mycobacterium smegmatis/pathogenicity , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/pathogenicity , Nitric Oxide/analysis , Pregnancy , Primary Cell Culture , Reactive Oxygen Species/analysis , Reactive Oxygen Species/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Umbilical Veins/cytology , Virulence/immunologyABSTRACT
La utilización de técnicas de ingeniería genética y biología molecular ha permitido aislar e identificar diferentes tipos virales asociados a diversas enfermedades. Tal es el caso del papilomavirus humano (PVH) al cual se ha mencionado como el candidato etiológico del cáncer cervicouterino (CaCu). En el presente trabajo se analizó la presencia de PVH tipos 6, 11, 16 y 18 en ADN de tejido obtenido en biopsias de un grupo de 70 pacientes del Instituto Nacional de Cancerología (INCan), con diagnóstico histológico de CaCu invasor. Mediante hibridación Southern-blot, se observó que 17 (24.3 por ciento) casos fueron positivos para secuencias de PVH 16 y en siete (10 por ciento) para PVH 18; en estas muestras no fueron detectadas secuencias para PVH 6 y 11. Los resultados obtenidos sugieren que los PVH 16 y 18 son poco frecuentes en nuestra población hospitalaria. Es necesario realizar estudios con otros tipos virales asociados a CaCu, como los tipos 31, 33 y 35, a fin de ampliar el espectro de detección de PVH. También es necesario continuar con la identificación de PVH con otras técnicas de biología molecular --como la reacciónde polimesasa en cadena-- para conocer mejor la distribución, la frecuencia y el tipo de infección de PVH en pacientes que acuden al INCan con CaCu.
