Pentraxin 3 Regulates miR‐21 Expression and Secretion in Brown Adipocytes During Lipopolysaccharide‐Induced Inflammation

Lin, Te-Yueh; Guo, Hong; Chen, Xiaoli

doi:10.1002/oby.22701

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…For example, 3 h of LPS treatment can significantly increase PTX3 expression and secretion in inguinal adipocytes but not brown adipocytes until 6 or 24 h of LPS stimulation. From current and previously published results (Lin et al 2020), white adipocytes are more responsive to secrete PTX3 under the LPS-induced inflammation, and macrophages may contribute to PTX3 production indirectly through releasing inflammatory factors in response to LPS stimulation. Although there was a negative correlation between circulating PTX3 level and BMI, PTX3 gene expression was elevated in visceral adipose tissue of obesity (Osorio-Conles et al 2011, Witasp et al 2014.…”

Section: Discussionmentioning

confidence: 79%

Unraveling mechanisms of pentraxin 3 secretion in adipocytes during inflammation

Lin

Guo

Chen

2021

Journal of Molecular Endocrinology

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Pentraxin 3 (PTX3) is a soluble pattern recognition receptor playing an important role in immune response and inflammation. Lipopolysaccharide (LPS) stimulation can significantly induce PTX3 expression and secretion in adipocytes. Appropriate regulation of PTX3 secretion is critical for inflammatory homeostasis. Using chemical inhibitors of conventional and unconventional protein secretion, we explored the mechanisms that control LPS-stimulated PTX3 secretion in 3T3-L1 adipocytes. Inhibiting the conventional protein secretion blocked LPS-stimulated PTX3 secretion, resulting in cellular PTX3 accumulation in adipocytes. We also detected PTX3 in exosomes from LPS-treated adipocytes; inhibiting exosome trafficking attenuated PTX3 secretion. However, only 4.3% of secreted PTX3 was detected in exosomes compared to 95.7% in non-exosomal fraction. The fractionation of isolated exosomes by the iodixanol density gradient centrifugation confirmed that a small portion of secreted PTX3 overlapped with exosomal markers in small extracellular-vesicle fractions. We conclude that PTX3 is secreted mainly through the conventional protein secretion and a small percentage of PTX3 is released in exosomes from LPS-stimulated adipocytes.

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Section: Discussionmentioning

confidence: 79%

Unraveling mechanisms of pentraxin 3 secretion in adipocytes during inflammation

Lin

Guo

Chen

2021

Journal of Molecular Endocrinology

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“…J774 cells were treated with lipopolysaccharide (LPS; Sigma-Aldrich #L6529) as a model of endotoxemia at a concentration of 1.0 μg/mL for a duration of 24 h prior to harvest. To determine the effect of LPS in vivo, RNA was isolated from the spleen of LPS- or PBS-treated 16 week old male C57/B6 mice, which had been harvested, frozen, and stored from a previous study [ 13 ]. Each animal received LPS at 0.3 mg/kg bodyweight or PBS intraperitoneally 6 h prior to sacrifice.…”

Section: Methodsmentioning

confidence: 99%

NCOA4 Regulates Iron Recycling and Responds to Hepcidin Activity and Lipopolysaccharide in Macrophages

et al. 2022

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Macrophages, via erythrophagocytosis, recycle iron from effete erythrocytes to newly developing red blood cells. Conversion of potentially cytotoxic levels of iron from its heme into nonheme form during iron recycling is safely accomplished via coordinated regulations of cellular iron transport and homeostasis. Herein, we demonstrate the roles and regulation of NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy in macrophages after erythrophagocytosis using the mouse macrophage cell line J774 cells. Ferritin in J774 cells increased with the rise of nonheme iron by erythrocyte ingestion and declined when total cellular iron contents subsequently decreased. NCOA4, a selective autophagic cargo receptor for ferritin, was responsible for the control of cellular ferritin and total iron contents at the later stage of erythrophagocytosis. A hepcidin analog, which limits the flux of iron through iron-recycling by inhibiting iron export at the plasma membrane, repressed NCOA4 expression and led to accumulation of ferritin in the mouse macrophages. Transcriptome analyses revealed a functional association of immune response with NCOA4-dependent gene expressions, and we confirmed repression of Ncoa4 by lipopolysaccharide (LPS) in J774 cells and the spleen of mice. Collectively, our studies indicate that NCOA4 facilitates cellular ferritin turnover and the release of iron by macrophages after erythrophagocytosis and functions as a regulatory target for molecular signals of systemic iron overload and inflammation. These identify macrophage NCOA4 as a potential therapeutic target for disorders of systemic iron dysregulation, including anemia of inflammation and hemochromatosis.

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“…[ 6 , 7 ] Atherosclerosis is considered as an immune-mediated inflammatory process. [ 8 , 9 ] Pentraxin 3 ( PTX3) is the earliest identified long normal pentameric protein and is a highly conserved family of orthomeric proteins with short normal pentameric protein C. [ 10 , 11 ] It plays an important role in innate immunity and inflammatory response and is closely related to the occurrence and development of atherosclerosis. It can also play a cardiovascular protective role by balancing immune inflammation.…”

Section: Introductionmentioning

confidence: 99%

Correlation between single nucleotide polymorphisms in the 3 primer untranslated region of PTX3 and the risk of essential hypertension

Chen¹,

Liu²,

Pan³

et al. 2021

Medicine

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The aim of this study was to investigate the correlation between single-nucleotide polymorphisms (SNPs) in the 3 primer of untranslated region (3’UTR) of the Pentraxin 3 ( PTX3 ) gene and the risk of essential hypertension (EHT). PTX3 genotypes, rs2614, rs111451363, and rs73158510 locus, were found in 260 patients with EHT and 260 healthy controls. Quantitative real-time polymerase chain reaction was used to detect plasma hsa-miR-4766-5p levels. Enzyme-linked immunosorbent assay was used to detect plasma PTX3 levels. The dual-luciferase reporter assay was used to identify the binding site of hsa-miR-4766-5p to the PTX3 . PTX3 rs2614 locus T allele was a high risk factor for EHT (odds ratio [OR] = 2.76, 95% confidence interval [CI]: 1.86–4.09, P < .01). Sex and diabetes history affected the correlation between PTX3 gene rs2614 locus SNP and EHT risk. The CCG haplotype was a protective factor for EHT (OR = 0.40, 95% CI: 0.28–0.57, P < .01), whereas the TCG haplotype was a risk factor for EHT (OR = 2.35, 95% CI: 1.51–3.66, P < .01). The plasma PTX3 level of patients with EHT was significantly higher than that of the control group, and the difference was statistically significant ( P < .01). The area under the curve for EHT diagnosis in plasma PTX3 levels was 0.62 (95% CI: 0.57–0.66, P < .01). The plasma hsa-miR-4766-5p level in patients with EHT was significantly lower than that in the control group ( P < .01). The area under the curve for the diagnosis of EHT according to the plasma hsa-miR-4766-5p level was 0.88 (95% CI: 0.85–0.91, P < .01). Plasma PTX3 levels were significantly negatively correlated with hsa-miR-4766-5p levels in patients with EHT and the control group ( r = −0.87, −0.85, P < .01, P < .01). The PTX3 gene rs2614 locus C allele was the target gene of hsa-miR-4766-5p. The PTX3 rs2614 locus SNP is significantly associated with EHT risk.

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Pentraxin 3 Regulates miR‐21 Expression and Secretion in Brown Adipocytes During Lipopolysaccharide‐Induced Inflammation

Cited by 3 publications

References 42 publications

Unraveling mechanisms of pentraxin 3 secretion in adipocytes during inflammation

Unraveling mechanisms of pentraxin 3 secretion in adipocytes during inflammation

NCOA4 Regulates Iron Recycling and Responds to Hepcidin Activity and Lipopolysaccharide in Macrophages

Correlation between single nucleotide polymorphisms in the 3 primer untranslated region of PTX3 and the risk of essential hypertension

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