scholarly journals Increased SERPINA3 Level Is Associated with Ulcerative Colitis

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2371
Author(s):  
Jingwei Zhang ◽  
Wei Wang ◽  
Shenglong Zhu ◽  
Yongquan Chen
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Drug Targets ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
Potential Drug ◽  
New Genes ◽  
Potential Biomarker ◽  
Pubmed Database

Ulcerative colitis (UC) is a recurrent, chronic intestinal disease that is currently incurable. Its pathogenesis remains to be further understood. Therefore, seeking new biomarkers and potential drug targets is urgent for the effective treatment of UC. In this study, the gene expression profile GSE38713 was obtained from the GEO (Gene Expression Omnibus) database. Data normalisation and screening of the differentially expressed genes (DEGs) were conducted using R software, and gene ontology (GO) enrichment was performed using Metascape online tools. The PubMed database was used to screen new genes that have not been reported, and SERPINA3 was selected. The correlation between SERPINA3 and other inflammatory factors was analysed by Spearman correlation analysis. Finally, colitis model mice and an in-vitro model were established to validate the function of the SERPINA3 gene. SERPINA3 gene expression was markedly increased in UC patient samples, colitis models and in-vitro models and showed an association with other inflammatory factors. ROC analysis indicated that SERPINA3 could represent a potential biomarker of active UC. Additionally, silencing SERPINA3 in an in-vitro intestinal epithelial inflammatory model significantly decreased the mRNA level of inflammatory factors. This study provides supportive evidence that SERPINA3 may act as a key biomarker and potential drug target in UC treatment.

scholarly journals The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382199528
Author(s):  
Qing Lv ◽  
Qinghua Xia ◽  
Anshu Li ◽  
Zhiyong Wang
Keyword(s):  
Tumor Microenvironment ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
Stomach Carcinoma ◽  
Downstream Target ◽  
Volume Weight

This study was performed to investigate the role of interleukin-1 receptor accessory protein (IL1RAP) in stomach carcinoma in vitro and in vivo, determine whether IL1RAP knockdown could regulate the development of stomach carcinoma, and elucidate the relationship between IL1RAP knockdown and inflammation by tumor microenvironment-related inflammatory factors in stomach carcinoma. We first used TCGA and GEPIA systems to predict the potential function of IL1RAP. Second, western blot and RT-PCR were used to analyze the expression, or mRNA level, of IL1RAP at different tissue or cell lines. Third, the occurrence and development of stomach carcinoma in vitro and in vivo were observed by using IL1RAP knockdown lentivirus. Finally, the inflammation of stomach carcinoma in vitro and in vivo was observed. Results show that in GEPIA and TCGA systems, IL1RAP expression in STAD tumor tissue was higher than normal, and high expression of IL1RAP in STAD patients had a worse prognostic outcome. Besides, GSEA shown IL1RAP was negative correlation of apopopsis, TLR4 and NF-κB signaling pathway. We also predicted that IL1RAP may related to IL-1 s, IL-33, and IL-36 s in STAD. The IL1RAP expression and mRNA level in tumor, or MGC803, cells were increased. Furthermore, IL1RAP knockdown by lentivirus could inhibit stomach carcinoma development in vitro and in vivo through weakening tumor cell proliferation, migration, invasion, therefore reducing tumor volume, weight, and biomarker levels, and increasing apoptotic level. Finally, we found IL1RAP knockdown could increase inflammation of tumor microenvironment-related inflammatory factors of stomach carcinoma, in vitro and in vivo. Our study demonstrates that IL1RAP is possibly able to regulate inflammation and apoptosis in stomach carcinoma. Furthermore, TLR4, NF-κB, IL-1 s, IL-33, and IL-36 s maybe the downstream target factor of IL1RAP in inflammation. These results may provide a new strategy for stomach carcinoma development by regulating inflammation.

Stabilization but no functional influence of HIF-1α expression in the intestinal epithelium during Salmonella Typhimurium infection

2022 ◽  
Author(s):  
Laura Robrahn ◽  
Aline Dupont ◽  
Sandra Jumpertz ◽  
Kaiyi Zhang ◽  
Christian H. Holland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intestinal Epithelium ◽  
Bacterial Infections ◽  
Inflammatory Diseases ◽  
Protein Stabilization ◽  
Inflammatory Factors ◽  
Intestinal Epithelial ◽  
Data Set ◽  
The Impact

The hypoxia-inducible transcription factor 1 (HIF-1) has been shown to enhance microbial killing and to ameliorate the course of bacterial infections. While the impact of HIF-1 on inflammatory diseases of the gut has been studied intensively, its function in bacterial infections of the gastrointestinal tract remains largely elusive. With the help of a publicly available gene expression data set, we could infer significant activation of HIF-1 after oral infection of mice with Salmonella Typhimurium. Immunohistochemistry and western blot analysis confirmed marked HIF-1α protein stabilization, especially in the intestinal epithelium. This prompted us to analyze conditional Hif1a -deficient mice to examine cell type-specific functions of HIF-1 in this model. Our results demonstrate enhanced non-canonical induction of HIF-1 activity upon Salmonella infection in the intestinal epithelium as well as in macrophages. Surprisingly, Hif1a deletion in intestinal epithelial cells did not impact on inflammatory gene expression, bacterial spread or disease outcome. In contrast, Hif1a deletion in myeloid cells enhanced intestinal Cxcl2 expression and reduced the cecal Salmonella load. In vitro , HIF-1α-deficient macrophages showed an overall impaired transcription of mRNA encoding pro-inflammatory factors, however, intracellular survival of Salmonella was not impacted by HIF-1α deficiency.

scholarly journals Peripheral Blood Based Discrimination of Ulcerative Colitis and Crohn’s Disease from Non-IBD Colitis by Genome-Wide Gene Expression Profiling

2011 ◽  
Vol 30 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Ferenc Sipos ◽  
Orsolya Galamb ◽  
Barnabás Wichmann ◽  
Tibor Krenács ◽  
Kinga Tóth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Peripheral Blood ◽  
Independent Set ◽  
Molecular Diagnostic ◽  
Blood Samples ◽  
Specificity And Sensitivity

A molecular diagnostic assay using easily accessible peripheral blood would greatly assist in the screening and diagnosis of ulcerative colitis (UC) and Crohn’s disease (CD). Transcriptional profiles in blood/biopsy samples from 12 UC (6/12), 9 CD (5/9), 6 non-inflammatory bowel disease (non-IBD) colitis (6/0), and 11 healthy (11/11) patients were assessed by Affymetrix HGU133Plus2.0 microarrays. Prediction analysis of microarrays, discriminant and ROC analyses were performed, the results were validated by RT-PCR and immunohistochemistry using also an independent set of samples (15 blood samples, 45 biopsies). A set of 13 transcripts was differentially expressed in IBD, non-IBD controls and healthy blood samples (100% specificity and sensitivity). Validated difference was found in 16 transcripts between UC, non-IBD and normal blood, and 4 transcripts between CD, non-IBD and normal samples. UC and CD blood cases could be also distinguished by 5 genes with 100% specificity and sensitivity. Some disease associated alterations in blood transcripts were also detected in colonic tissue. IBD subtypes may be discriminated from non-IBD (diverticulitis, infective and ischemic colitis)in vitrofrom peripheral blood by screening for differential gene expression revealed in this study. Transcriptional profile alterations in peripheral blood can be located in diseased colon.

scholarly journals Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia

2019 ◽  
Vol 20 (2) ◽  
pp. 325 ◽  
Author(s):  
Jessica Kronenberg ◽  
Kaweh Pars ◽  
Marina Brieskorn ◽  
Chittappen Prajeeth ◽  
Sandra Heckers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Indirect Effects ◽  
Protein Level ◽  
Mannose Receptor ◽  
Inflammatory Factors ◽  
Primary Metabolite ◽  
Proliferation And Differentiation ◽  
Anti Inflammatory ◽  
Relapsing Remitting Multiple Sclerosis

Dimethylfumarate (DMF) has been approved the for treatment of relapsing-remitting multiple sclerosis. The mode of action of DMF and its assumed active primary metabolite monomethylfumarate (MMF) is still not fully understood, notably for brain resident cells. Therefore we investigated potential direct effects of DMF and MMF on microglia and indirect effects on oligodendrocytes. Primary rat microglia were differentiated into M1-like, M2-like and M0 phenotypes and treated in vitro with DMF or MMF. The gene expression of pro-inflammatory and anti-inflammatory factors such as growth factors (IGF-1), interleukins (IL-10, IL-1β), chemokines (CCl3, CXCL-10) as well as cytokines (TGF-1β, TNFα), iNOS, and the mannose receptor (MRC1) was examined by determining their transcription level with qPCR, and on the protein level by ELISA and FACS analysis. Furthermore, microglia function was determined by phagocytosis assays and indirect effects on oligodendroglial proliferation and differentiation. DMF treatment of M0 and M1-like polarized microglia demonstrated an upregulation of gene expression for IGF-1 and MRC1, but not on the protein level. While the phagocytic activity remained unchanged, DMF and MMF treated microglia supernatants led to an enhanced proliferation of oligodendrocyte precursor cells (OPC). These results suggest that DMF has anti-inflammatory effects on microglia which may result in enhanced proliferation of OPC.

scholarly journals Blockage of tropoelastin secretion by monensin represses tropoelastin synthesis at a pretranslational level in rat smooth muscle cells.

1985 ◽  
Vol 5 (1) ◽  
pp. 253-258 ◽  
Author(s):  
S M Frisch ◽  
J M Davidson ◽  
Z Werb
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Genomic Dna ◽  
Mrna Level ◽  
In Vitro Translation ◽  
Aortic Smooth Muscle Cell ◽  
Aortic Smooth Muscle ◽  
Reported Effect ◽  
Ca 50

The blockage of protein secretion in the R22 cultured rat aortic smooth muscle cell strain with monensin repressed tropoelastin gene expression at the mRNA level by ca. 50-fold as measured by biosynthetic pulse-labeling, in vitro translation, and hybridization with a tropoelastin genomic DNA probe. These results suggest that tropoelastin gene expression is autoregulated, and they represent the first reported effect of monensin on gene expression.

scholarly journals Intrusion of a DNA Repair Protein in the RNome World: Is This the Beginning of a New Era?

2009 ◽  
Vol 30 (2) ◽  
pp. 366-371 ◽  
Author(s):  
Gianluca Tell ◽  
David M. Wilson ◽  
Chow H. Lee
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Mrna Level ◽  
Rna Metabolism ◽  
Coding Region ◽  
Control Of Gene Expression ◽  
Dna And Rna ◽  
New Findings

ABSTRACT Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is known to be involved in base excision DNA repair, acting as the major abasic endonuclease; the protein also functions as a redox coactivator of several transcription factors that regulate gene expression. Recent findings highlight a novel role for APE1 in RNA metabolism. The new findings are as follows: (i) APE1 interacts with rRNA and ribosome processing protein NPM1 within the nucleolus; (ii) APE1 interacts with proteins involved in ribosome assembly (i.e., RLA0, RSSA) and RNA maturation (i.e., PRP19, MEP50) within the cytoplasm; (iii) APE1 cleaves abasic RNA; and (iv) APE1 cleaves a specific coding region of c-myc mRNA in vitro and influences c-myc mRNA level and half-life in cells. Such findings on the role of APE1 in the posttranscriptional control of gene expression could explain its ability to influence diverse biological processes and its relocalization to cytoplasmic compartments in some tissues and tumors. In addition, we propose that APE1 serves as a “cleansing” factor for oxidatively damaged abasic RNA, establishing a novel connection between DNA and RNA surveillance mechanisms. In this review, we introduce questions and speculations concerning the role of APE1 in RNA metabolism and discuss the implications of these findings in a broader evolutionary context.

scholarly journals Modulation of Borrelia burgdorferi Stringent Response and Gene Expression during Extracellular Growth with Tick Cells

2002 ◽  
Vol 70 (6) ◽  
pp. 3061-3067 ◽  
Author(s):  
Julia Bugrysheva ◽  
Elena Y. Dobrikova ◽  
Henry P. Godfrey ◽  
Marina L. Sartakova ◽  
Felipe C. Cabello
Keyword(s):  
Gene Expression ◽  
Borrelia Burgdorferi ◽  
Cell Lines ◽  
Mrna Level ◽  
Stringent Response ◽  
Global Regulator ◽  
Tick Cell ◽  
Fourfold Increase ◽  
Reciprocal Interactions

ABSTRACT Borrelia burgdorferi N40 multiplied extracellularly when it was cocultured with tick cells in L15BS medium, a medium which by itself did not support B. burgdorferi N40 growth. Growth of B. burgdorferi N40 in the presence of tick cells was associated with decreased production of (p)ppGpp, the stringent response global regulator, a fourfold decrease in relA/spoT mRNA, an eightfold net decrease in bmpD mRNA, and a fourfold increase in rpsL-bmpD mRNA compared to growth of B. burgdorferi in BSK-H medium. As a result, the polycistronic rpsL-bmpD mRNA level increased from 3 to 100% of the total bmpD message. These observations demonstrate that there are reciprocal interactions between B. burgdorferi and tick cells in vitro and indicate that the starvation-associated stringent response mediated by (p)ppGpp present in B. burgdorferi growing in BSK-H medium is ameliorated in B. burgdorferi growing in coculture with tick cell lines. These results suggest that this system can provide a useful model for identifying genes controlling interactions of B. burgdorferi with tick cells in vitro when it is coupled with genetic methods to isolate and complement B. burgdorferi mutants.

scholarly journals P048 Mucosal macrophages express elevated levels of HDAC9 in inflamed and uninflamed mucosa of Crohn’s disease, but not ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S157-S157
Author(s):  
M Ghiboub ◽  
J de Bruyn ◽  
K Reedquist ◽  
T Radstake ◽  
C Wichers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Histone Deacetylases ◽  
Cell Function ◽  
Mrna Level ◽  
Critical Role ◽  
Histone Deacetylation ◽  
Inflamed Tissue

Abstract Background Histone deacetylases (HDACs) are a group of enzymes that control histone and non-histone deacetylation and influence inflammatory gene transcription. Certain members of the HDAC family control the function of macrophages and play an important role in immune response. In this study, we aimed to study the expression of HDACs in mucosal macrophages isolated from inflammatory bowel diseases (IBD) patients. Methods Both macroscopically inflamed and non-inflamed colon resection tissue were collected from 15 Crohn’s disease (CD) and nine ulcerative colitis (UC) patients operated on for therapy refractory disease. Of the CD patients, 53% had ileal and 47% ileocolonic disease. Of the UC patients, 44% had left-sided colitis and 56% pancolitis. Lamina propria was separated from the muscularis externa, and a targeted array for epigenetic enzymes was performed. To assess the relevance of HDAC9 gene expression in terms of protein level, immunofluorescence staining of HDAC9 protein was undertaken in tissue sections from inflamed and non-inflamed mucosa. CD68 was used as a pan-macrophage marker. Results From our array, expression of HDAC9 was significantly higher in the inflamed mucosa of CD patients compared with UC patients (p = 0.005). Gene expression of HDAC9 in non-inflamed mucosa from CD was elevated compared with non-inflamed mucosa from UC. In addition, in CD, HDAC9 mRNA level was increased in inflamed tissue in comparison to non-inflamed tissue (p = 0.046). In conjunction with the expression data, HDAC9 protein was found highly expressed in inflamed tissue. HDAC9 was predominantly localised in the cytoplasmic compartment of macrophages in non-inflamed tissue whilst HDAC9 localised to the nucleus of macrophages in inflamed tissue. Conclusion HDAC9 is member of class IIA HDAC superfamily that exerts pro-inflammatory properties. The inhibition of HDAC9 in experimental murine colitis clearly enhances regulatory T-cell function, suggesting a critical role for HDAC9 in breaching immune homeostasis (de Zoeten EF et al, 2009). We suggest here that HDAC9 can serve as an additional marker to distinguish CD from UC in tissue biopsies. Furthermore, we show for the first time that HDAC9 protein is expressed in mucosal macrophages of CD patients, indicating its potential in mediating macrophage inflammatory function in IBD. Further studies are currently being undertaken to elucidate the role of HDAC9 in CD pathogenesis.

Pharmacological Inhibition of K-Cl Cotransport Alters In Vitro Maturation of Normal and β-Thalassemic Human Erythroid Progenitors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3819-3819
Author(s):  
Lucia De Franceschi ◽  
Luisa Ronzoni ◽  
Achille Iolascon ◽  
Francesca Cimmino ◽  
Seth L. Alper ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Growth ◽  
Protein Expression ◽  
Mrna Level ◽  
Cell Volume Regulation ◽  
Erythroid Cell ◽  
Cell Counts ◽  
Normal Controls

Abstract The K-Cl cotransporter family (KCC) plays a crucial role in cell volume regulation, and KCC1 and KCC3 have been reported to participate in cell growth events (Shen MR, PNAS98, 2001; Shen MR JBC278, 2003). Expression of KCC1, KCC3 and KCC4 has been reported in erythroid cells. In β-thalassemic red blood cells (RBCs), K-Cl cotransport activity is abnormally activated and contributes to red cell loss of water and K. This study evaluated the gene expression of two KCC gene products and the effects of the KCC inhibitor [(dihydroindoenyl)oxy]alkanoic acid (DIOA) on in vitro liquid-culture expansion of human normal and β thalassemic (β thal) erythroid precursors from peripheral blood CD34+ cells. Cells from normal subjects and from β thalassemia major patients (cod39cod39) were cultured for 7 days (to the pro-normobast stage) and 14 days (to the eythroblast stage) in the presence or absence of 10 mM DIOA, At each time point the following parameters were evaluated; cells counts; cytospins stained with Wright-Giemsa to assess differential cell counts and morphology, cell cycle stage by fluorescence-activated cell sorting after propidium iodide staining; KCC protein expression by Western-blot analysis with antibody to the shared KCC carboxy-terminus; mRNA by real time-PCR analysis. KCC protein expression increased during erythropoiesis in both normal and β thal cells, and was higher in β thal cells than in normal controls. KCC1 mRNA level was increased only in β thal cells at day 14, whereas KCC3 mRNA level was increased at day 14 in both normal and β thal cells. DIOA significantly reduced the number of both normal and β thal cells, parallelled by increases in the percentage of polychromatophilic normoblasts among normal progenitors and of basophilic normoblasts among b thal progenitors. We further investigated the inhibitory effects of DIOA on cell growth by FACS evaluation of cell cycle distributions and by determination ofCycD, p21, Casp3 and Casp8 gene expression. At day 14 DIOA exposure was associated with: significant reduction in the percentage of β thal cells in S-phase compared to either untreated cells or DIOA-treated normal controls; up-regulation of CycD gene expression in both normal and β thal cells; down-regulation of p21 in β thal cells; up-regulation of casp3 and casp8 in both normal and β thal cells. These data suggest that KCC is involved in the late phase of erythropoiesis mainly in β thal cells, and support a novel role of KCC in erythroid cell growth.

scholarly journals Flux Analysis of the Trypanosoma brucei Glycolysis Based on a Multiobjective-Criteria Bioinformatic Approach

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Amine Ghozlane ◽  
Frédéric Bringaud ◽  
Hayssam Soueidan ◽  
Isabelle Dutour ◽  
Fabien Jourdan ◽  
...  
Keyword(s):  
Experimental Data ◽  
Glucose Metabolism ◽  
Metabolic Network ◽  
Trypanosoma Brucei ◽  
Drug Targets ◽  
Flux Analysis ◽  
Insect Vector ◽  
Procyclic Form ◽  
New Genes

Trypanosoma brucei is a protozoan parasite of major of interest in discovering new genes for drug targets. This parasite alternates its life cycle between the mammal host(s) (bloodstream form) and the insect vector (procyclic form), with two divergent glucose metabolism amenable to in vitro culture. While the metabolic network of the bloodstream forms has been well characterized, the flux distribution between the different branches of the glucose metabolic network in the procyclic form has not been addressed so far. We present a computational analysis (called Metaboflux) that exploits the metabolic topology of the procyclic form, and allows the incorporation of multipurpose experimental data to increase the biological relevance of the model. The alternatives resulting from the structural complexity of networks are formulated as an optimization problem solved by a metaheuristic where experimental data are modeled in a multiobjective function. Our results show that the current metabolic model is in agreement with experimental data and confirms the observed high metabolic flexibility of glucose metabolism. In addition, Metaboflux offers a rational explanation for the high flexibility in the ratio between final products from glucose metabolism, thsat is, flux redistribution through the malic enzyme steps.

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