*MMP1* bimodal expression and differential response to inflammatory mediators is linked to promoter polymorphisms
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ABSTRACT:
PROVIDER: PRJNA131673 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE23068: Gene expression profiling of HUVEC under basal (resting) conditions GSE23069: Gene expression profiling of HUVEC after stimulation with an inflammatory mediator cocktail Refer to individual Series
2011-07-19 | E-GEOD-23070 | biostudies-arrayexpress
Project description:Identifying the functional importance of the millions of single nucleotide polymorphisms (SNPs) in the human genome is a difficult challenge. Therefore, a reverse strategy, which identifies functionally important SNPs by virtue of the bimodal abundance across the human population of the SNP-related mRNAs will be useful. Those mRNA transcripts that are expressed at two distinct abundances in proportion to SNP allele frequency may warrant further study. Matrix metalloproteinase 1 (MMP1) is important in both normal development and in numerous pathologies. Although much research has been conducted to investigate the expression of MMP1 in many different cell types and conditions, the regulation of its expression is still not fully understood.In this study, we used a novel but straightforward method based on agglomerative hierarchical clustering to identify bimodally expressed transcripts in human umbilical vein endothelial cell (HUVEC) microarray data from 15 individuals. We found that MMP1 mRNA abundance was bimodally distributed in un-treated HUVECs and showed a bimodal response to inflammatory mediator treatment. RT-PCR and MMP1 activity assays confirmed the bimodal regulation and DNA sequencing of 69 individuals identified an MMP1 gene promoter polymorphism that segregated precisely with the MMP1 bimodal expression. Chromatin immunoprecipitation (ChIP) experiments indicated that the transcription factors (TFs) ETS1, ETS2 and GATA3, bind to the MMP1 promoter in the region of this polymorphism and may contribute to the bimodal expression.We describe a simple method to identify putative bimodally expressed RNAs from transcriptome data that is effective yet easy for non-statisticians to understand and use. This method identified bimodal endothelial cell expression of MMP1, which appears to be biologically significant with implications for inflammatory disease. (271 Words).
| S-EPMC3040839 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-07-20 | GSE23070 | GEO
Project description:Staphylococcus warneri strain:MMP1 Genome sequencing and assembly
| PRJNA304162 | ENA
Project description:Recently, we reported on the associations of seven single nucleotide polymorphisms (SNPs) in the promoter region of MMP1 gene with susceptibility to cutaneous melanoma (CM). Considering the reported correlation between MMP1 expression and melanoma progression, we hypothesized that these promoter SNPs might affect CM progression and prognosis. In this study, we examined the associations of seven SNPs with overall survival, as well as six clinicopathological factors in 754 patients with CM. After adjustment for 11 covariates, we observed significant associations of the SNP -422A>T (rs475007) with ulceration status (P=0.012), primary tumor thickness (P=0.040), and anatomic site (P=0.030). We also observed significant associations of the SNP -755T>G (rs498186) with ulceration status (P=0.038) and anatomic site (P=0.003). Two SNPs, -839G>A and -519A>G, were marginally associated with primary tumor thickness, ulceration status, and anatomic site. Furthermore, the frequency of haplotype 2G-G-G-A-A-G-T was higher in patients with ulceration (odds ratio=2.18, 95% confidence interval: 1.08-4.40, P=0.030) compared with those without ulceration. However, we did not find significant associations of these SNPs with overall survival and other clinical factors. As primary tumor thickness and ulceration status are two important indicators of tumor progression and have significant associations with melanoma prognosis, our results suggested that these promoter SNPs in MMP1 might have potential effects on melanoma progression and prognosis by influencing related clinical factors.
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Project description:Traumatic brain injury (TBI) caused by external mechanical forces is a major health burden worldwide, but the underlying mechanism in glia remains largely unclear. We report herein that Drosophila adults exhibit a defective blood-brain-barrier (BBB), elevated innate immune responses, and appear to be hypertrophy of astrocytes upon consecutive strikes with a high-impact trauma device. RNA sequencing (RNA-seq) analysis of these astrocytes revealed upregulated expression of genes encoding PDGF and VEGF receptor-related (Pvr, a receptor tyrosine kinase (RTK)), adaptor protein complex 1 (AP-1, a transcription factor complex of the c-Jun N-terminal Kinase (JNK) pathway) composed of Jun-related antigen (Jra) and kayak (kay), and matrix metalloproteinase 1 (Mmp1) following TBI. Interestingly, Pvr is both required and sufficient for AP-1 and Mmp1 upregulation, while knockdown of AP-1 expression in the background of Pvr overexpression in astrocytes rescued Mmp1 upregulation upon TBI, indicating that Pvr acts as the upstream receptor for the downstream AP-1–Mmp1 transduction. Moreover, dynamin-associated endocytosis was found to be an important regulatory step in downregulating Pvr signaling. Our results identify a new Pvr–AP-1–Mmp1 signaling pathway in astrocytes in response to TBI, providing potential targets for developing new therapeutic strategies of TBI.
2024-06-30 | GSE263447 | GEO
Project description:Gene expression can be highly heterogeneous in clonal cell populations. An extreme type of heterogeneity is the so-called bistable or bimodal expression, whereby a cell can differentiate into two alternative expression states, and consequently a population will be composed of cells that are ‘ON’ and cells that are ‘OFF’. Stochastic fluctuations of protein levels, also referred to as noise, provide the necessary source of heterogeneity that must be amplified by autostimulatory feedback regulation to obtain the bimodal response. A classical model of bistable differentiation is the development of genetic competence in Bacillus subtilis. Noise in expression of the transcription factor ComK ultimately determines the fraction of cells that enter the competent state. Due to its intrinsic random nature, noise is difficult to investigate. We adapted an artificial autostimulatory loop that bypasses all known ComK regulators, to screen for possible factors that affect noise in the bimodal regulation of ComK. This led to the discovery of Kre, a novel factor that controls the bimodal expression of ComK. Kre appears to affect the stability of comK mRNA. Interestingly, ComK itself represses the expression of kre, adding a new double negative feedback loop to the intricate ComK regulation circuit. Our data emphasize that mRNA stability is an important factor in bimodal regulation.
2017-02-10 | GSE61757 | GEO
Project description:Specific genes or encoded proteins are involved in regulating various learning models of different species through certain signaling pathways，but whether there are also regulatory genes during bimodal learning and memory is largely unknown. Using a multi-omics approach to examine gene expression changes in bees brain performed with three different learning assays, a general up-regulation of genes and proteins were observed in bimodal learning compared to controls. Protein-protein network predictions of differential proteins together with FISH assays suggest ALDH7A1 may be involved in regulation of bimodal learning and memory. Injecting siRNA-ALDH7A1 to the bee brain results in significant inhibition the expressions of ALDH7A1 and regucalcin, and increase β-alanine content. Interestingly, we found that loss of ALDH7A1 only affect visual-olfactory bimodal learning and memory, but not single visual or olfactory conditioned learning after ALDH7A1-RNAi in bees. Therefore, our data suggests that ALDH7A1 may affect bimodal learning and memory though controlling β-alanine related plasticity mechanisms.
2021-09-13 | PXD017008 | Pride
Project description:Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. Current treatments are insufficient in improving the prognosis of lung cancer patients with comorbid idiopathic pulmonary fibrosis (IPF-LC). Senescent fibroblasts play a pivotal role within the tumor microenvironment, influencing tumor progression by secreted exosomes. With evidence that fibroblast senescence is an important mechanism of IPF, we sought to investigate the impact of senescent IPF lung fibroblast-derived exosomes on non-small cell lung cancer (NSCLC). Our results show that IPF fibroblasts (diseased human lung fibroblasts, DHLF) express significant senescence markers, promoting NSCLC proliferation, invasion, and epithelial-mesenchymal transition. Specifically, we observed senescent DHLFs secret more exosomes (DHLF-exosomes), which could enhance proliferation and colony-forming ability of cancer cells. Proteomic analysis of DHLF-exosomes identified upregulation of SASP factors, notably MMP1, which activates the surface receptor PAR1. Knocking down MMP1 or using PAR1 inhibitors reduced the tumor-promoting effects of DHLF-exosomes in vivo and in vitro. Mechanistically, MMP1 acted via activating the PI3K-AKT-mTOR pathway. In conclusion, our results suggest that exosomal MMP1 derived from senescent IPF fibroblasts promotes NSCLC proliferation and colony formation by targeting PAR1 and activating the PI3K-AKT-mTOR pathway. These findings provide a novel therapeutic approach for patients with IPF-LC.
2024-10-21 | GSE279637 | GEO
Project description:To cope with sudden changes in their environment, bacteria can use a bet-hedging strategy by dividing the population into cells with different properties. This so called bimodal or bistable cellular differentiation is generally controlled by positive feedback regulation of transcriptional activators. Due to continued turnover of the cytoplasmic content, it is difficult for these activators to reach an activation threshold concentration when cells are growing exponentially. This is one reason why bimodal differentiation is primarily observed from the onset of the stationary phase when exponential growth ceases. An exception is the bimodal induction of motility in Bacillus subtilis, which occurs early during exponential growth. Several mechanisms have been put forward to explain this, including double negative-feedback regulation and the stability of the mRNA molecules involved. In this study, we used fluorescence-assisted cell sorting to compare the transcriptome of motile and non-motile cells and noted that expression of ribosomal genes is lower in motile cells. This was confirmed using an unstable GFP reporter fused to the strong ribosomal rpsD promoter. We propose that the reduction in ribosomal gene expression in motile cells is the result of a diversion of cellular resources to the synthesis of the chemotaxis and motility systems. In agreement, single-cell microscopic analysis indicates that motile cells are slightly shorter than non-motile cells, an indication of slower growth. We speculate that this growth rate reduction can contribute to the bimodal induction of motility during exponential growth.
2021-01-20 | GSE164348 | GEO