Multiple Polymorphisms Affect Expression and Function of the Neuropeptide S Receptor - NPSR1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: marco zucchelli
PROVIDER: E-MEXP-3226 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:BACKGROUND: neuropeptide S (NPS) and its receptor NPSR1 act along the hypothalamic-pituitary-adrenal axis to modulate anxiety, fear responses, nociception and inflammation. The importance of the NPS-NPSR1 signaling pathway is highlighted by the observation that, in humans, NPSR1 polymorphism associates with asthma, inflammatory bowel disease, rheumatoid arthritis, panic disorders, and intermediate phenotypes of functional gastrointestinal disorders. Because of the genetic complexity at the NPSR1 locus, however, true causative variations remain to be identified, together with their specific effects on receptor expression or function. To gain insight into the mechanisms leading to NPSR1 disease-predisposing effects, we performed a thorough functional characterization of all NPSR1 promoter and coding SNPs commonly occurring in Caucasians (minor allele frequency >0.02). PRINCIPAL FINDINGS: we identified one promoter SNP (rs2530547 [-103]) that significantly affects luciferase expression in gene reporter assays and NPSR1 mRNA levels in human leukocytes. We also detected quantitative differences in NPS-induced genome-wide transcriptional profiles and CRE-dependent luciferase activities associated with three NPSR1 non-synonymous SNPs (rs324981 [Ile107Asn], rs34705969 [Cys197Phe], rs727162 [Arg241Ser]), with a coding variant exhibiting a loss-of-function phenotype (197Phe). Potential mechanistic explanations were sought with molecular modelling and bioinformatics, and a pilot study of 2230 IBD cases and controls provided initial support to the hypothesis that different cis-combinations of these functional SNPs variably affect disease risk. SIGNIFICANCE: these findings represent a first step to decipher NPSR1 locus complexity and its impact on several human conditions NPS antagonists have been recently described, and our results are of potential pharmacogenetic relevance.
| S-EPMC3244468 | biostudies-literature
Project description:The purpose of this study was to identify downstream gene targets regulated by Neuropeptide S Receptor 1 (NPSR1) upon NPS stimulation. To do this we used human epithelial kidney (HEK)-293H cell lines stable transfected with NPSR1-A and stimulated with NPS for 6 hours. Two controls were used: NPS stimulated HEK-293H cells and unstimulated NPSR1-A cells.
2006-08-24 | E-MEXP-829 | biostudies-arrayexpress
Project description:To define the sequence of events that lead to the generation of somatic motor neurons (MNs), we took advantage of ESCs, which can be directed to differentiate into spinal neural progenitors (NPs) in vitro (Gouti et al. 2014). This method relies on the exposure of ESCs, cultured as a monolayer, to a brief pulse of Wnt signalling prior to neural induction. Subsequently, removal of Wnt signalling and exposure to retinoic acid (RA) results in the generation of NPs. Exposure of these NPs to Shh signalling agonist SAG induces the expression of genes expressed in the ventral spinal cord and the induction of MNs.
2018-02-01 | E-MTAB-5466 | biostudies-arrayexpress
Project description:Poly-ethylene-glycol (PEG)-based nanoparticles (NPs) - including cylindrical micelles (CNPs), spherical micelles (SNPs), and PEGylated liposomes (PLs) - are hypothesized to be cleared in vivo by opsonization followed by liver macrophage phagocytosis. This hypothesis has been used to explain the rapid and significant localization of NPs to the liver after administration into the mammalian vasculature. Here, we show that the opsonization-phagocytosis nexus is not the major factor driving PEG-NP – macrophage interactions. First, mouse and human blood proteins had insignificant affinity for PEG-NPs. Second, PEG-NPs bound macrophages in the absence of serum proteins. Third, lipoproteins blocked PEG-NP binding to macrophages. Because of these findings, we tested the postulate that PEG-NPs bind (apo)lipoprotein receptors. Indeed, PEG-NPs triggered an in vitro macrophage transcription program that was similar to that triggered by lipoproteins and different from that triggered by lipopolysaccharide (LPS) and group A Streptococcus. Unlike LPS and pathogens, PLs did not increase transcripts involved in phagocytosis or inflammation. High-density lipoprotein (HDL) and SNPs triggered remarkably similar mouse bone-marrow-derived macrophage transcription programs. Unlike opsonized pathogens, CNPs, SNPs, and PLs lowered macrophage autophagosome levels and either reduced or did not increase the secretion of key macrophage pro-inflammatory cytokines and chemokines. Thus, the sequential opsonization and phagocytosis process is likely a minor aspect of PEG-NP – macrophage interactions. Instead, PEG-NP interactions with (apo)lipoprotein and scavenger receptors appear to be a strong driving force for PEG-NP – macrophage binding, entry, and downstream effects. We hypothesize that the high presence of these receptors on liver macrophages and on liver sinusoidal endothelial cells is the reason PEG-NPs localize rapidly and strongly to the liver. To investigate the response of macrophages to nanoparticles, we incubated PEGylated liposomes (PLs), spherical nanoparticles (SNPs), high-density lipoproteins (HDL), low-density lipoproteins (LDL), Group A Streptococcus pathogens (JRS4), and lipopolysaccharide (LPS) with RAW264.7 and primary bone-marrow derived mouse macrophages
2023-12-27 | GSE249596 | GEO
Project description:Background and Purpose: Genome-wide association studies significantly link intracranial aneurysm (IA) to single-nucleotide polymorphisms (SNPs) in six genomic loci. To gain insight into the relevance of these IA associated SNPs, we aimed to identify regulatory regions and analyze overall gene expression in the human circle of Willis (CoW), on which these aneurysms develop. Methods: We performed chromatin immunoprecipitation and sequencing for histone modifications H3K4me1 and H3K27ac to identify regulatory regions, including distal enhancers and active promoters, in post mortem specimens of the human CoW. These experiments were complemented with RNA sequencing on the same specimens. We determined whether these regulatory regions overlap with IA associated SNPs, using computational methods. By combining our results with publicly available data, we investigated the effect of IA associated SNPs on the newly identified regulatory regions and linked them to potential target genes. Results: We find that IA associated SNPs are significantly enriched in CoW regulatory regions. Some of the IA associated SNPs that overlap with a regulatory region are likely to alter transcription factor binding, and in proximity to these regulatory regions are 102 genes that are expressed in the CoW. In addition, gene expression in the CoW is enriched for genes related to cell adhesion and the extracellular matrix. Conclusions: CoW regulatory regions link IA associated SNPs to genes with a potential role in the development of IAs. Our data refine previous predictions on SNPs associated with IA and provide a substantial resource from which candidates for follow-up studies can be prioritized.
2018-01-04 | GSE107196 | GEO
Project description:FLAG-hPHF3 was transiently expressed in human HEK293 cells, followed by anti-FLAG immunoprecipitation, on-bead digest and NanoLC-MS analysis.
2022-02-17 | PXD026292 | Pride
Project description:Exposure to titanium dioxide (TiO2) food additive by ingestion increased over the years. TiO2 is used in food to give a brighter, fresher colour to sweets, cookies, salad dressing under the name E171. New studies on E171 showed that after ingestion in a colorectal cancer mouse model, a significant increased number of colorectal tumours were found. In addition, short-term exposure to E171 induces gene expression changes in relation to oxidative stress responses, an impairment of the immune system, activation of signalling and cancer-related genes. Furthermore, dysregulation of the immune system was also observed after ingestion of E171 in rats. E171 comprises nanoparticles (NPs) and microparticles (MPs). Previous in vitro studies showed the capacity of E171, TiO2 NPs and MPs to induce oxidative stress, DNA damage, and induction of the micronuclei. The aim of our study was to investigate the relative contribution of the NPs and MPs fractions to the effects of E171 at the molecular level. This investigation was performed using in vitro exposure of Caco-2 cells to E171 as well as the NPs and MPs fractions of TiO2 and assessing effects with genome wide gene expression analysis. Results showed that the E171, TiO2 NPs and MPs induce gene expression changes in signalling, inflammation, immune system, transport, and cancer. Contribution of NPs was observed on genes involved in TLR cascade, MHC class I and II presentation, late cornified envelope, potassium channels, and cell cycle. MPs contribution was observed with changes in gene expression on a target to Hedgehog family, α-defensins, cadherin and cholinergic receptors. The gene expression changes associated with the immune system and inflammation induced by E171, MPs, and NPs suggest the creation of a favourable environment for cancer development.
2019-11-22 | GSE110410 | GEO
Project description:HEK293 Flp-In cells were transfected transiently with various SLC22A10 orthologs, including human, chimpanzee, and the mutations to proline or leucine at position 220. After 72 hours of transfection, cell pellets were collected. The quantification was performed on both HEK293 cells and HEK293cells expressing the different SLC22A10 orthologs and mutations
2024-04-09 | PXD047102 | Pride
Project description:This project aimed to assess the toxicity underlying the exposure of Turbot (Scophthalmus maximus), an economically valuable fish species, to TiO2 and Ag nanoparticles (NPs). To carry out the study, juvenile fish were exposed to TiO2 and Ag NPs incorporated in the diet. After 14 days of exposure fish were euthanized and liver and kidney samples collected for proteomics. The shotgun proteomics analysis revealed quantitative changes in multiple proteins. The results suggest effects of TiO2 and Ag NPs in energy/lipid metabolism and for instance alterations in ribosome functions, protein biosynthesis and related processes. This proteomic study provided as well candidate biomarkers for NPs exposure in aquaculture species.
2022-10-18 | PXD037420 | Pride
Project description:Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift (EMSA) and luciferase reporter assays. To identify binding of transcription factors and/or other nuclear proteins in an allele-determined manner, we employed pulldown using nuclear extract from Daudi cells and silver staining in SNPs that had exhibited allele-specific differential binding by EMSA. Each pulldown product for each allele of the five high-probability SNPs (rs2297550 C/G, rs13213604 C/G, rs276461 T/C, rs9907955 C/T, rs7302634 T/C) was evaluated by mass spectrometry (MS) to identify binding nuclear proteins, yielding a set of candidate proteins for each.
2024-08-02 | PXD048367 | Pride