The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor

Estrada, Sarah M.; Thagard, Andrew S.; DeHart, Mary; Damicis, Jennifer; Dornisch, Elisabeth; Ippolito, Danielle L.; Burd, Irina; Napolitano, Peter G.; Ieronimakis, Nicholas

doi:10.1038/s41419-019-2196-7

Cited by 16 publications

(10 citation statements)

References 78 publications

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“…Recently, it was found that alkaline ceramidase 3 (ACER3) mediated palmitic-acid-induced oxidative stress and played the pathological role in NASH. Targeting ACER3 could alleviate the severity of NASH by suppressing the hepatocellular oxidative stress, thus attenuating early inflammation and fibrosis but not steatosis, demonstrated by the similar area of steatosis and significantly reduced number of inflammatory foci, lower expression levels of IL-6, TNF-α and TGF-β, and minor fibrosis in Acer3 −/− mice ( 146 ). Oxidized phospholipids (OxPLs) accumulated and induced oxidative stress and mitochondrial damage in NASH.…”

Section: Metabolic Regulation Of Innate Immune Responsesmentioning

confidence: 99%

Roles of Hepatic Innate and Innate-Like Lymphocytes in Nonalcoholic Steatohepatitis

Chen

Tian

2020

Front. Immunol.

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Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease (NAFLD), is accompanied by steatosis, hepatocyte injury and liver inflammation, which has been a health problem in the world as one of the major high risk factors of cirrhosis and hepatocellular carcinoma (HCC). Complex immune responses involving T cells, B cells, Kupffer cells, monocytes, neutrophils, DCs and other innate lymphocytes account for the pathogenesis of NASH; however, the underlying mechanisms have not been clearly elucidated in detail. In the liver, innate and innate-like lymphocytes account for more than two-thirds of total lymphocytes and play an important role in maintaining the immune homeostasis. Therefore, their roles in the progression of NASH deserves investigation. In this review, we summarized murine NASH models for immunological studies, including the diet-induced NASH, chemical-induced NASH and genetic-induced NASH. The role of innate and innate-like lymphocytes including NK cells, ILCs, NKT, γδT and MAIT cells in the progression of NASH were elucidated. Further, the metabolic regulation of the innate immune response was addressed in consideration to explain the molecular mechanisms. Based on the findings of the reviewed studies, strategies of immune intervention are proposed to control the progression of NASH.

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Section: Metabolic Regulation Of Innate Immune Responsesmentioning

confidence: 99%

Roles of Hepatic Innate and Innate-Like Lymphocytes in Nonalcoholic Steatohepatitis

Chen

Tian

2020

Front. Immunol.

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“… 14 LncRNA HCP5 could abrogate the anti-tumour effect of 5-FU in in vivo assays of nude mice, thus indicating that HCP5 may represent a new therapeutic target for GC. 45 LncRNA HOTTIP is upregulated in 5-FU resistant cells, and downregulation of this lncRNA could markedly reduce the 50% inhibitory concentration of 5-FU in GC cells. 25 GC patients with high expression of lncRNA HULC often show poor prognosis; silencing of this lncRNA could reverse chemoresistance by inducing apoptosis in GC cells.…”

Section: Resultsmentioning

confidence: 99%

“… 44 LncRNA HCP5 drives fatty acid oxidation through the miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote the stemness and OXA resistance of GC. 45 Mesenchymal stem cells secrete TGF-β1 and induce lncRNA MACC1-AS1 expression in GC cells, thereby promoting the latter’s stemness and OXA resistance. 46 LncRNA MALAT1 contributes to OXA resistance in GC cells by downregulating miR-22-3p and upregulating ZFP91.…”

Section: Resultsmentioning

confidence: 99%

“…LncRNA ANRIL, HCP5, MACC1-AS1 and XLOC_006753 are involved in DDP (or OXA) and 5-FU resistance by upregulating MDR1 and MRP1, regulating the miR-3619-5p/AMPK/PGC1α/CEBPB axis, promoting fatty acid oxidation and antagonising miR-145-5p, and inducing cell proliferation as well as reducing apoptosis through the PI3K/AKT/mTOR pathway, respectively. 12 , 41 , 45 , 46 LncRNA XIST promotes the chemoresistance of ADR and DDP by upregulating MDR1 and MRP1. 40 LncRNA ZFAS1 could induce the chemoresistance of DDP and PTX by activating the Wnt/β-catenin signalling pathway.…”

Section: Resultsmentioning

confidence: 99%

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Role of Long Non-Coding RNAs in the Chemoresistance of Gastric Cancer: A Systematic Review

Li¹,

Lü²,

Zhou³

et al. 2021

OTT

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Purpose: Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play a vital role in the chemoresistance of gastric cancer (GC). The present systematic review summarises the emerging role, potential targets or pathways and regulatory mechanisms of lncRNAs involved in chemoresistance and proposes a number of clinical implications of lncRNAs as novel therapeutic targets for GC. Methods: Studies on lncRNAs involved in the chemoresistance of GC published until July 2020 in the PubMed and Web of Science databases were systematically reviewed and the expression form, role in chemoresistance, targets or pathways, corresponding drugs and potential mechanisms of relevant lncRNAs were summarised in detail. Results: A total of 48 studies were included in this systematic review. Amongst these studies, 32 involved single drug resistance and 16 involved in multidrug resistance (MDR). The 48 studies collected described 38 lncRNAs in the drug-resistant cells of GC, including 33 upregulated and 5 downregulated lncRNAs. Cisplatin (DDP) was the most studied drug and lncRNA MALAT1 was the most studied lncRNA related to the chemoresistance of GC. The potential mechanisms of chemoresistance for lncRNAs in GC mainly included, amongst others, reduction of apoptosis, induction of autophagy, repair of DNA damage, promotion of epithelial-mesenchymal transition (EMT) and regulation of the related signalling pathways. Conclusion:LncRNAs play a vital role in the chemoresistance of GC and are novel therapeutic targets for the disease. Detailed chemoresistance mechanisms, translational studies and clinical trials on lncRNAs in GC are urgently needed.

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“…NR4A1 is a molecule with diverse biologic functions, including regulation of inflammation in the central nervous system, heart, and lung (4)(5)(6)(7)(8)(9)(10)(11). Specifically, NR4A1 is a factor in macrophage development and inflammatory response through polarization and transcriptional regulation (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

A Novel Role for the Nuclear Receptor, NR4A1, inKlebsiella pneumoniaeLung Infection

Partyka

Henkel

Campfield

2020

Preprint

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Klebsiella pneumoniae is a Gram-negative bacterial pathogen and common cause of pneumonia and bacteremia. Increasingly, K. pneumoniae has become a public health concern due to its rate of nosocomial infection and emerging, broad-spectrum antibiotic resistance. The nuclear receptor NR4A1 exhibits functionality in a multitude of organ systems and is implicated as having a role in the immune response to bacterial infection, though its role in K. pneumoniae infection is unknown. To determine if Nr4a1 functions in response to K. pneumoniae pulmonary disease, we infected wild-type and Nr4a1-/- mice with K. pneumoniae and assessed bacterial growth, immune cell recruitment and function, and cytokine production. We found that Nr4a1-/- mice had increased bacterial burden in the lungs and spleen, though no differences in cell recruitment. Pro-inflammatory cytokines, Il1β and Il6, as well as chemokine, Cxcl2, were significantly decreased in the BAL fluid cells of Nr4a1-/- mice 5 hours post-infection. Additionally, Nr4a1-/- mice had reduced IL-1β and myeloperoxidase protein production. We then examined the bactericidal function of macrophages and neutrophils from WT and Nr4a1-/- mice. We identified that Nr4a1-/- neutrophils had decreased bactericidal function compared to wild-type neutrophils, which was associated with reduced expression of Il1β, Lcn2, Mpo, and Lyz2. These data suggest Nr4a1 plays a novel and essential role in neutrophil function during the host immune response to K. pneumoniae pulmonary infection.

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The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor

Cited by 16 publications

References 78 publications

Roles of Hepatic Innate and Innate-Like Lymphocytes in Nonalcoholic Steatohepatitis

Roles of Hepatic Innate and Innate-Like Lymphocytes in Nonalcoholic Steatohepatitis

Role of Long Non-Coding RNAs in the Chemoresistance of Gastric Cancer: A Systematic Review

A Novel Role for the Nuclear Receptor, NR4A1, inKlebsiella pneumoniaeLung Infection

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