TNFAIP2 Inhibits Early TNFa-Induced NF-&amp;#954;B Signaling and Decreases Survival in Septic Shock Patients

Thair, Simone A.; Topchiy, Elena; Boyd, John H.; Cirstea, Mihai; Wang, Catherine; Nakada, Taka‐aki; Fjell, Christopher D.; Wurfel, Mark M.; Russell, James A.; Walley, Keith R.

doi:10.1159/000437330

Cited by 21 publications

(19 citation statements)

References 42 publications

(41 reference statements)

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“…In VSMC module 31 we identified 14 genes ( APOLD1, MT1A, ZFP36, EGR1, JUNB, FOSB, JUN, FOS, RERGL, MT1M, DNAJB1, CCNH, HSPA1B and HSPA1A ) whose expression was significantly upregulated in PA cells and with strong network connectivity. Among these genes we identify immediate-early (IE) genes ZFP36, EGR1, JUNB, FOSB and FOS as critical response genes in this hallmark process which cluster tightly together and correlate with NFKBIA and TNFAIP2 - both inhibitors of NFkB-mediated signaling 58 (Extended Data Fig. 6c).…”

Section: Resultsmentioning

confidence: 99%

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Alsaigh¹,

Evans²,

Frankel

et al. 2020

Preprint

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Atherogenesis involves an interplay of inflammation, tissue remodeling and cellular transdifferentiation (CTD), making it especially difficult to precisely delineate its pathophysiology. Here we examine the single-cell transcriptome of entire atherosclerotic core (AC) plaques and patient-matched proximal adjacent (PA) portions of carotid artery tissue from patients undergoing carotid endarterectomy. We use a novel tissue dissociation strategy, single-cell RNA sequencing, and systems-biology approaches to analyze the transcriptional profiles of six main cell populations and identify key gene drivers of pathogenic biological processes in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). Our results reveal an anatomic continuum whereby PA cells promote and respond to inflammatory processes and eventually transition through CTD into matrix-secreting cells in the AC. Inflammatory signaling in PA ECs is driven by IL6, while TNFa signaling defines inflammation in both PA ECs and VSMCs. Furthermore, we identify POSTN, SPP1 and IBSP in AC VSMCs, and ITLN1, SCX and S100A4 in AC ECs as key drivers of CTD in the atherosclerotic core. These results establish an anatomic framework for atherogenesis and suggest a site-specific strategy for disruption of disease progression.

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Section: Resultsmentioning

confidence: 99%

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Alsaigh¹,

Evans²,

Frankel

et al. 2020

Preprint

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“…IGF2 is present in follicular fluid and has recently been shown to promote malignant transformation in immortalized TE cell lines (Hsu et al, 2019). TNFAIP2 is thought to be involved in inflammatory angiogenesis and has been reported to down regulate NF-κB (Jia et al, 2018;Thair et al, 2015). If we suppose TNFAIP2 has a role in controlling NF-κB signaling in the TE, we would expect to see NF-κB signaling activity to be reduced in the proximal TE.…”

Section: Discussionmentioning

confidence: 99%

WNT and inflammatory signaling distinguish human Fallopian tube epithelial cell populations

Rose

Bidarimath

Webster

et al. 2020

Preprint

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A substantial fraction of ovarian/extra-uterine high-grade serous carcinomas (HGSCs) likely originate in the distal region of the Fallopian tube's epithelium (TE) before implanting/metastasizing to the ovary. Unfortunately, molecular and cellular mechanisms rendering preferential cancer susceptibility of the human distal TE remain insufficiently elucidated, largely due to limited primary human TE gene expression data. Here we report an in depth bioinformatic characterization of 34 primary TE cell mRNA-seq samples.These samples were prepared from the proximal and distal TE regions of 12 normal Fallopian tubes. TE cells were segregated based on their aldehyde dehydrogenase (ALDH) activity. As compared to the proximal TE, cells from the distal region form organoids with higher frequency and larger size during serial organoid formation assays. Consistent with enrichment for organoid-forming stem/progenitor cells, ALDH+ cells have greater WNT signaling activity. Comparative evaluation of proximal and distal TE cell population's shows heightened inflammatory signaling in distal differentiated (ALDH-) TE.Furthermore, comparisons of proximal and distal TE cell populations finds that the distal TE express gene sets characteristic of four HGSC molecular sub-types, and that distal ALDH+ cell populations exhibit greater enrichment than their ALDH-counterparts. Taken together, our study shows that increased organoid forming capacity, WNT and inflammatory signaling, and HGSC signatures underlie the differences between distal and proximal regions of the human TE. These findings provide the basis for further mechanistic studies of distal TE susceptibility to the malignant transformation.

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“…16 In vitro experiments, TNFAIP2 used to be differentially expressed in blood vessels, and it maybe an inhibitor of NF-κB or an auto-inhibitor of TNF-α response. 17 TNFAIP2 can also serve as a target gene for retinoic acid and play an important role in inducing apoptosis in acute promyelocytic leukemia and multiple tumors. 18 Some studies have demonstrated that TNFAIP2 can regulate inflammation and angiogenesis, induce apoptosis, promote cell proliferation, adhesion, migration and invasion, and mediate the formation of membrane nanotubes by NF-κB signaling pathway, Retinoic acid signaling pathway and Kruppel-like factor 5 (KLF5) signaling pathway.…”

Section: Physiological Functions and Mechanisms Of Tnfaip2mentioning

confidence: 99%

<p>Tumor Necrosis Factor Alpha-Induced Proteins in Malignant Tumors: Progress and Prospects</p>

Guo¹,

Yuan²

2020

OTT

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Tumor necrosis factor (TNF) is the first cytokine used in tumor biotherapy, but TNFrelated drugs are limited by the lack of specific targets. Tumor necrosis factor alpha-induced proteins (TNFAIPs), derived from TNF, is a protein family and participates in proliferation, invasion and metastasis of tumor cells. In order to better understand biological functions and potential roles of TNFAIPs in malignant tumors, this paper in the form of "Gene-Protein-Tumor correlation" summarizes the biological characteristics, physiological functions and mechanisms of TNFAIPs by searching National Center of Biotechnology Information, GeneCards, UniProt and STRING databases. The relationship between TNFAIPs and malignant tumors is analyzed, and protein-protein interaction diagram in members of TNFAIPs is drawn based on TNF for the first time. We find that TNF as a key factor is related to TNFAIP1, TNFAIP3, TNFAIP5, TNFAIP6, TNFAIP8 and TNFAIP9, which can be directly involved in activating TNFAIP1, TNFAIP5, TNFAIP8 and TNFAIP9. We confirm that the mechanism of TNFAIP1, TNFAIP2 and TNFAIP3 inducing tumors may be related to NF-κB signaling pathway, but the mechanism of tumor induction by other members of TNFAIPs is not clear. In the future, translational studies are needed to explore the mechanisms of TNF-TNFAIPs-tumors.

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TNFAIP2 Inhibits Early TNFa-Induced NF-κB Signaling and Decreases Survival in Septic Shock Patients

Cited by 21 publications

References 42 publications

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

WNT and inflammatory signaling distinguish human Fallopian tube epithelial cell populations

<p>Tumor Necrosis Factor Alpha-Induced Proteins in Malignant Tumors: Progress and Prospects</p>

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