RESUMO
A mouse model of acute lung injury (ALI) was chosen in this study to explore the key genes and pathways involved in the process of ALI with microarray technology. Gene expression microarray data were downloaded from the Gene Expression Omnibus database. Mice from the experimental group were further divided into 6 subgroups, which received octadecenoate treatments for 1, 1.5, 3, 4, 18, and 24 h. Differentially co-expressed genes were screened to uncover the pathogenesis of ALI. Almost all of the differentially co-expressed genes were identified at two times: 1.5 and 3 h. Functional analysis revealed that several inflammation-related pathways were significantly enriched. Ubiquitin-mediated proteolysis, hematopoietic cell lineage, and leukocyte transendothelial migration were enriched at 1.5 h. The B cell receptor signaling pathway, T cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, Fc epsilon RI signaling pathway, and ubiquitin-mediated proteolysis were significantly enriched at 3 h. It could be inferred that ALI initiated at 1.5 h and lasted through 3 h. However, co-expression patterns were not found from 4 h onward. In conclusion, several key genes and pathways implicated in the development of ALI were found in this study using the mouse model, among which ubiquitin-mediated proteolysis appears to play an important role in the process.
Assuntos
Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/patologia , Transdução de Sinais , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Mapeamento de Interação de Proteínas , Proteólise , Ácidos Esteáricos/metabolismo , Ubiquitina/metabolismoRESUMO
The purpose of this study was to identify critical genes associated with septic multiple trauma by comparing peripheral whole blood samples from multiple trauma patients with and without sepsis. A microarray data set was downloaded from the Gene Expression Omnibus (GEO) database. This data set included 70 samples, 36 from multiple trauma patients with sepsis and 34 from multiple trauma patients without sepsis (as a control set). The data were preprocessed, and differentially expressed genes (DEGs) were then screened for using packages of the R language. Functional analysis of DEGs was performed with DAVID. Interaction networks were then established for the most up- and down-regulated genes using HitPredict. Pathway-enrichment analysis was conducted for genes in the networks using WebGestalt. Fifty-eight DEGs were identified. The expression levels of PLAU (down-regulated) and MMP8 (up-regulated) presented the largest fold-changes, and interaction networks were established for these genes. Further analysis revealed that PLAT (plasminogen activator, tissue) and SERPINF2 (serpin peptidase inhibitor, clade F, member 2), which interact with PLAU, play important roles in the pathway of the component and coagulation cascade. We hypothesize that PLAU is a major regulator of the component and coagulation cascade, and down-regulation of PLAU results in dysfunction of the pathway, causing sepsis.
Assuntos
Regulação da Expressão Gênica , Traumatismo Múltiplo/genética , Mapas de Interação de Proteínas/genética , Sepse/genética , Humanos , Metaloproteinase 8 da Matriz/biossíntese , Traumatismo Múltiplo/complicações , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Sepse/complicações , Ativador de Plasminogênio Tipo Uroquinase/biossínteseRESUMO
Hepatitis B virus S protein (HBs) plays an important role in hepatocellular carcinoma progression. However, to date, no direct and effective methods exist to research the function of HBs. Here, we combined the technology of RNA interference with recombinant adenovirus, constructed a recombinant adenovirus-expressing small hairpin RNA of HBs, and infected HepG2.2.15 cells. Then, reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR, enzyme-linked immunosorbent assay, and Western blot analysis were performed to verify the interference effects. As a result, a recombinant adenovirus was successfully constructed and effectively packaged in AD293 cells, and it significantly inhibited HBs mRNA and protein expression in vitro. Our study may provide a novel tool to study HBs function.
Assuntos
Regulação Viral da Expressão Gênica , Vírus da Hepatite B/genética , Proteína S/genética , RNA Interferente Pequeno/genética , Adenoviridae/genética , Células Hep G2 , Vírus da Hepatite B/patogenicidade , Humanos , Proteína S/isolamento & purificação , RNA Mensageiro/biossínteseRESUMO
Osteoporosis is a heritable disease characterized mainly by low bone mineral density (BMD) and/or osteoporotic fractures (OF). Most genome-wide association studies on osteoporosis have focused on BMD, whereas little effort has been expended to identify genetic variants directly linked to OF. To determine whether BMD-loci are also associated with OF risk, we performed a validation study to examine 23 BMD-loci reported by recent genome-wide association studies for association with hip OF risk. Our sample consisted of 700 elderly Chinese Han subjects, 350 with hip OF and 350 healthy matched controls. We identified four BMD-loci that were significantly associated with hip OF in this Chinese population, including 7q21 (FLJ42280, P = 1.17 × 10(-4) for rs4729260; P = 0.008 for rs7781370), 6p21 (MHC, P = 0.004 for rs3130340), 13q14 (TNFSF11, P = 0.012 for rs9533090; P = 0.018 for rs9594759; P = 0.020 for rs9594738; P = 0.044 for rs9594751), and 18q21 (TNFRSF11A, P = 0.015 for rs884205). The SNP rs4729260 at 7q21 remained significantly associated, even after conservative Bonferroni's correction. Our results further highlight the importance of these loci in the pathogenesis of osteoporosis, and demonstrate that it is feasible and useful to use OF as the direct phenotype to conduct genetic studies, to enhance our understanding of the genetic architecture of osteoporosis.