Endoplasmic reticulum stress (ERS) is a cellular defensive response to restore homeostasisand reduce the protein load. Over-activation of ERS can induce cell differentiation, proliferation, apoptosis, and autophagy. MicroRNAs (miRNAs) are endogenous non-coding RNAs (ncRNAs) thatregulate the expression of key proteins and genes in the ERS signaling pathway through post-transcriptional action. Meanwhile, activated ERS signaling pathway can indirectly regulate the expressionand function of target genes by decreasing miRNA stability. Based on a brief introduction of ERS classicalsignaling pathways, this paper further elaborated how microRNAs regulate ERS signaling pathways topromote apoptosis and proliferation, and what effect they would have on the expression profile of diseasesbased on this association. We also summarize the regulation of ERS on miRNAs expression and thecurrent research status. The mutual regulation between the two could provide a new idea for the follow-upresearch on the therapeutic targets of diseases.

The microRNA (miRNA) regulation mechanisms associated with atherosclerosis are largely undocumented. Specific selection and efficient validation of miRNA regulation pathways involved in atherosclerosis development may be better assessed by contemporary microarray platforms applying cross-verification methodology. A screening platform was established using both miRNA and genomic microarrays. Microarray analysis was then simultaneously performed on pooled atherosclerotic aortic tissues from 10 Apolipoprotein E (apoE) knockout mice (apoE-/-) and 10 healthy C57BL/6 (B6) mice. Differentiated miRNAs were screened and cross-verified against an mRNA screen database to explore integrative mRNA-miRNA regulation. Gene set enrichment analysis was conducted to describe the potential pathways regulated by these mRNA-miRNA interactions. High-throughput data analysis of miRNA and genomic microarrays of knockout and healthy control mice revealed 75 differentially expressed miRNAs in apoE-/- mice at a threshold value of 2. The six miRNAs with the greatest differentiation expression were confirmed by real-time quantitative reverse-transcription PCR (qRT-PCR) in atherosclerotic tissues. Significantly enriched pathways, such as the type 2 diabetes mellitus pathway, were observed by a gene-set enrichment analysis. The enriched molecular pathways were confirmed through qRT-PCR evaluation by observing the presence of suppressor of cytokine signaling 3 (SOCS3) and SOCS3-related miRNAs, miR-30a, miR-30e and miR-19b. Cross-verified high-throughput microarrays are optimally accurate and effective screening methods for miRNA regulation profiles associated with atherosclerosis. The identified SOCS3 pathway is a potentially valuable target for future development of targeted miRNA therapies to control atherosclerosis development and progression.
Animals ; Aorta/metabolism/pathology ; Apolipoproteins E/*deficiency/metabolism ; Atherosclerosis/genetics/pathology ; Down-Regulation/genetics ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/*genetics/metabolism ; Models, Biological ; *Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/*genetics ; Suppressor of Cytokine Signaling Proteins/genetics/metabolism ; Up-Regulation/genetics

BACKGROUNDThe genome of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) includes sequences encoding the putative protein X4 (ORF8, ORF7a), consisting of 122 amino acids. The deduced sequence contains a probable cleaved signal peptide sequence and a C-terminal transmembrane helix, indicating that protein X4 is likely to be a type I membrane protein. This study was conducted to demonstrate whether the protein X4 was expressed and its essential function in the process of SARS-CoV infection.

METHODSThe prokaryotic and eukaryotic protein X4-expressing plasmids were constructed. Recombinant soluble protein X4 was purified from E. coli using ion exchange chromatography, and the preparation was injected into chicken for rising specific polyclonal antibodies. The expression of protein X4 in SARS-CoV-infected Vero E6 cells and lung tissues from patients with SARS was performed using immunofluorescence assay and immunohistochemistry technique. The preliminary function of protein X4 was evaluated by treatment with and over-expression of protein X4 in cell lines. Western blot was employed to evaluate the expression of protein X4 in SARS-CoV particles.

RESULTSWe expressed and purified soluble recombinant protein X4 from E.coli, and generated specific antibodies against protein X4. Western blot proved that the protein X4 was not assembled in the SARS-CoV particles. Indirect immunofluorescence assays revealed that the expression of protein X4 was detected at 8 hours after infection in SARS-CoV-infected Vero E6 cells. It was also detected in the lung tissues from patients with SARS. Treatment with and overexpression of protein X4 inhibited the growth of Balb/c 3T3 cells as determined by cell counting and MTT assays.

CONCLUSIONThe results provide the evidence of protein X4 expression following SARS-CoV infection, and may facilitate further investigation of the immunopathological mechanism of SARS.

Amino Acid Sequence ; Animals ; BALB 3T3 Cells ; Cercopithecus aethiops ; Growth Inhibitors ; analysis ; physiology ; HeLa Cells ; Humans ; Immunohistochemistry ; Lung ; chemistry ; Mice ; Molecular Sequence Data ; SARS Virus ; chemistry ; Severe Acute Respiratory Syndrome ; metabolism ; Vero Cells ; Viral Structural Proteins ; analysis ; physiology

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications