BackgroundEpithelial-to-Mesenchymal Transition (EMT) induced by glucose in human peritoneal mesothelial cells (HPMCs) is a major cause of peritoneal membrane (PM) fibrosis and dysfunction.MethodsTo investigate serum response factor (SRF) impacts on EMT-derived fibrosis in PM, we isolated HPMCs from the effluents of patients with end-stage renal disease (ESRD) to analyze alterations during peritoneal dialysis (PD) and observe the response of PM to SRF in a rat model.ResultsOur results demonstrated the activation and translocation of SRF into the nuclei of HPMCs under extensive periods of PD. Accordingly, HPMCs lost their epithelial morphology with a decrease in E-cadherin expression and an increase in α-smooth muscle actin (α-SMA) expression, implying a transition in phenotype. PD with 4.25% glucose solution significantly induced SRF up-regulation and increased peritoneal thickness. In immortal HPMCs, high glucose (HG, 60 mmol/L) stimulated SRF overexpression in transformed fibroblastic HPMCs. SRF-siRNA preserved HPMC morphology, while transfection of SRF plasmid into HPMCs caused the opposite effects. Evidence from electrophoretic mobility shift, chromatin immunoprecipitation and reporter assays further supported that SRF transcriptionally regulated Snail, a potent inducer of EMT, by directly binding to its promoter.ConclusionsOur data suggested that activation of SRF/Snail pathway might contribute to the progressive PM fibrosis during PD.
Neutrophil-to-lymphocyte ratio (NLR) is commonly considered a useful prognostic index for many cardiovascular diseases; however, it has limited sensitivity and specificity. Factors associated with elevated NLR may aid in the prediction of prognosis with heart failure (HF) in combination with NLR. The present study sought to identify decisive factors associated with NLR in HF patients and investigate their association with elevated NLR. The gene expression profile for blood samples from 197 individuals with chronic heart failure (CHF), with corresponding hematological parameters and clinical data were obtained from the public database, GSE77343. Differentially expressed genes (DEGs) were identified, and Gene Ontology and pathway enrichment analyses were performed. The protein-protein interaction network was constructed with the Search Tool for the Retrieval of Interacting Genes along with Cytoscape. Receiver operating characteristic curves for predictive power, sensitivity and specificity were constructed. The present study identified specific associated DEGs by using Pearson linear correlation and logistic regression analysis. A mean NLR of 3.96 was determined as the cutoff value in the analysis. In total, 31 genes were initially identified as DEGs associated with elevated NLR. They were mainly enriched in neutrophil activation and neutrophil mediated immunity, in fluid shear stress and atherosclerosis, and transcriptional misregulation in cancer. Three focused DEGs, solute carrier family 22 member 4 (SLC22A4), interleukin-1 receptor 2 (IL1R2) and vanin 3 (VNN3), were finally revealed to be independently associated with elevated NLR in CHF patients. The present study demonstrated that the three genes SLC22A4, IL1R2 and VNN3 may be independently associated with elevated NLR in CHF patients as potential decisive factors of NLR.
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