HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease

Knyazev, E N; Maltseva, D. V.; Raygorodskaya, Maria; Shkurnikov, M. Yu.

doi:10.3389/fgene.2021.791640

Cited by 17 publications

(17 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Examination of DEGs and functional enrichment analysis revealed the LVBRS toolkit successfully recapitulated previously reported results [14]. Specifically, most DEGs in each study are the same (Table 3).…”

Section: Resultssupporting

confidence: 78%

“…Using the LVBRS toolkit to reanalyze publicly available data, we recapitulated previously published results [14] and added additional biological insights by incorporating additional functional databases and alternative splicing analysis. For example, both studies identified the MSig term "HALLMARK_TNFA_SIGNALING_VIA_NFKB" to be enriched among DEGs.…”

Section: Discussionmentioning

confidence: 93%

“…The LVBRS toolkit is open-source; thus, users can modify steps as needed using the Latch software development kit (https://docs.latch.bio/) and still benefit from a cloud-based infrastructure. To demonstrate the utility of this workflow, we reanalyzed publicly available RNA-Seq data examining the impact of severe and mild hypoxia induced by Cobalt (II) Chloride (CoCl 2 ) and oxyquinoline (Oxy) treatment, respectively, on a human colon adenocarcinoma cell line [14]. LVBRS successfully recapitulated major findings.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Latch Verified Bulk-RNA Seq toolkit: a cloud-based suite of workflows for bulk RNA-seq quality control, analysis, and functional enrichment

Le¹,

Steenwyk

Manske³

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Analysis of high-throughput bulk RNA-sequencing (RNA-seq) data reveals changes in gene expression between diverse conditions. Many tools have emerged to quality control RNA-seq reads, quantify expression levels, conduct functional enrichment among differentially expressed genes, or identify differential RNA splicing. However, unified toolkits for conducting these analyses are lacking. Moreover, existing software does not use cloud-based platforms that provide the necessary storage and computational resources to process RNA-seq data or intuitive graphical interfaces for easy use by experimental and computational scientists. Results To address these challenges, we introduce the Latch Verified Bulk RNA-Seq (LVBRS) toolkit, a flexible suite of programs packaged into a single workflow coupled with a graphical user interface for conducting quality control, transcript quantification, differential splicing, differential expression analysis, and functional enrichment analyses. For functional enrichment, the LVBRS toolkit supports three databases - Gene Ontology, KEGG Pathway, and Molecular Signatures database - capturing diverse functional information. We demonstrate the utility of the LVBRS toolkit by reanalyzing a publicly available dataset examining the impact of severe and mild models of hypoxia - induced by Cobalt (II) Chloride (CoCl2) and oxyquinoline treatment, respectively - on a human colon adenocarcinoma cell line. Our analyses reveal CoCl2 treatment results in more differentially expressed genes, recapitulating previously reported results that CoCl2 models more severe hypoxia. Moreover, including alternative splicing and functional enrichment analysis using a greater breadth of functional databases revealed additional biological insights - such as greater alternative splicing in the CoCl2 condition and differentially expressed DNA repair pathways. These results demonstrate the LVBRS toolkit's efficacy in facilitating biological insights from bulk RNA-seq data. Conclusions The LVBRS toolkit offers a robust unified framework for processing and analyzing Bulk RNA-Seq experiments. The easy-to-use graphical user interface will enable diverse scientists to conduct high-throughput bulk RNA-Seq analysis efficiently. Our aim is that the LVBRS toolkit will help streamline bulk RNA-seq workflows and facilitate deriving biologically meaningful insights from bulk RNA-seq data. The source code is freely available under the MIT license and hosted on the LatchBio Console (https://console.latch.bio/se/bulk-rnaseq), complete with documentation (https://latch.wiki/bulk-rna-seq-end-to-end).

show abstract

Section: Resultssupporting

confidence: 78%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Latch Verified Bulk-RNA Seq toolkit: a cloud-based suite of workflows for bulk RNA-seq quality control, analysis, and functional enrichment

Le¹,

Steenwyk

Manske³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…It was reported that more HIF-1α and NFATc1 were expressed in hypoxic conditions ( 39 , 40 ). NFATc1 activation was dependent on HIF, and NFATc1 was upregulated in hypoxia ( 41 ). In the present study, HIF-1α was highly expressed in PD-1 + CD4 T cells after P. yoelii infection ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

PD-1+ CD4 T cell immune response is mediated by HIF-1α/NFATc1 pathway after P. yoelii infection

Wei

Xie

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

The morbidity and mortality of malaria are still high. Programmed cell death-1(PD-1) is an important co-inhibitory factor and CD8 T cells with PD-1 were reported to be exhausted cells. It remains unknown what the role of CD4 T cells expressing PD-1 is and what the upstream regulating molecules of PD-1 in CD4 T cells are. The C57BL/6 mice were injected with Plasmodium yoelii (P. yoelii) in this study. Expressions of PD-1, activation markers, and cytokines were tested. The differentially expressed genes between PD-1+/- CD4 T cells were detected by microarray sequencing. Western blot, chromatin immunoprecipitation (ChIP), siRNA, hypoxia inducible factor-1α (HIF-1α) inducer and inhibitor were used to explore PD-1’s upstream molecules, respectively. The proportions of PD-1+ CD4 T cells increased post P. yoelii infection. PD-1+ CD4 T cells expressed more activated surface markers and could produce more cytokines. Nuclear factor of activated T cells 1 (NFATc1) was found to be a key transcription factor to induce PD-1 expression after infection. Both the inducer and the inhibitor of HIF-1α could change the expressions of NFATc1 and PD-1 in vivo and in vitro, respectively. Taken together, P. yoelii infection induced NFATc1 expression by HIF-1α. The highly expressed NFATc1 entered the nucleus and initiated PD-1 expression. PD-1+ CD4 T cells appeared to be more activated and could secrete more cytokines to regulate the host’s immune responses against malaria.

show abstract

“…After inflammation occurs, PLAUR binds to PLAU and activates plasminogen to plasmin, promoting inflammatory cell migration and activation and matrix metallopeptidase (MMP) activation, thereby participating in the inflammatory response ( 60 , 63 – 65 ). In addition, PLAUR can be regulated by the hypoxia-inducible factor HIF-1 to play a role in the hypoxia-related mechanisms of the disease ( 66 ). In this study, TIMP1 and PLAUR upregulation in ICH was validated in an independent cohort, which confirms the involvement of TIMP1 and PLAUR in ICH development.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia- and Inflammation-Related Transcription Factor SP3 May Be Involved in Platelet Activation and Inflammation in Intracranial Hemorrhage

Wan

Feng²,

Wang³

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

The purpose of this study was to identify the biomarkers implicated in the development of intracranial hemorrhage (ICH) and potential regulatory pathways. In the transcriptomic data for patients with ICH, we identified DEmiRNAs and DEmRNAs related to hypoxia, inflammation, and their transcription factors (TFs). An ICH-based miRNA-TF-mRNA regulatory network was thus constructed, and four biomarkers (TIMP1, PLAUR, DDIT3, and CD40) were screened for their association with inflammation or hypoxia by machine learning. Following this, SP3 was found to be a transcription factor involved in hypoxia and inflammation, which regulates TIMP1 and PLAUR. From the constructed miRNA-TF-mRNA regulatory network, we identified three axes, hsa-miR-940/RUNX1/TIMP1, hsa-miR-571/SP3/TIMP1, and hsa-miR-571/SP3/PLAUR, which may be involved in the development of ICH. Upregulated TIMP1 and PLAUR were validated in an independent clinical cohort 3 days after ICH onset. According to Gene Set Enrichment Analysis (GSEA), SP3 was discovered to be important in interleukin signaling and platelet activation for hemostasis. Transcription factor SP3 associated with hypoxia or inflammation plays an important role in development of ICH. This study provides potential targets for monitoring the severity of inflammation and hypoxia in patients with ICH.

show abstract

HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease

Cited by 17 publications

References 76 publications

Latch Verified Bulk-RNA Seq toolkit: a cloud-based suite of workflows for bulk RNA-seq quality control, analysis, and functional enrichment

Latch Verified Bulk-RNA Seq toolkit: a cloud-based suite of workflows for bulk RNA-seq quality control, analysis, and functional enrichment

PD-1+ CD4 T cell immune response is mediated by HIF-1α/NFATc1 pathway after P. yoelii infection

Hypoxia- and Inflammation-Related Transcription Factor SP3 May Be Involved in Platelet Activation and Inflammation in Intracranial Hemorrhage

Contact Info

Product

Resources

About