Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

Watanabe, Ryoji; Sato, Yuki; Ozawa, Nana; Takahashi, Yasuhiro; Koba, Shinji; Watanabe, Takuya

doi:10.3390/ijms19020465

Cited by 16 publications

(11 citation statements)

References 54 publications

(91 reference statements)

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“…Here, we found the IL10 gene and its receptor (IL10RA) upregulated in HFD piglets receiving the T3 diet, probably indicating an improvement of the inflammatory profile of SAT in obese animals derived from the ingestion of these bioactive ingredients. In close support with our view, other genes with anti-inflammatory effects such as TNF alpha induced protein 6 (TNFAIP6) 60 and TNF alpha induced protein 3 (TNFAIP3) 61 were also identified as upregulated in supplemented piglets.…”

Section: Discussionsupporting

confidence: 85%

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity

Ballester

Quintanilla

Ortega

et al. 2020

Sci Rep

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Global prevalence of obesity has increased to epidemic proportions over the past 40 years, with childhood obesity reaching alarming rates. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a high-calorie diet and supplemented with bioactive ingredients. A total of 43 nine-weeks-old animals distributed in four pens were fed with four different dietary treatments for 10 weeks: a conventional diet; a western-type diet; and a western-type diet with Bifidobacterium breve and rice hydrolysate, either adding or not omega-3 fatty acids. Animals fed a western-type diet increased body weight and total fat content and exhibited elevated serum concentrations of cholesterol, whereas animals supplemented with bioactive ingredients showed lower body weight gain and tended to accumulate less fat. An RNA-seq experiment was performed with a total of 20 animals (five per group). Differential expression analyses revealed an increase in lipogenesis, cholesterogenesis and inflammatory processes in animals on the western-type diet while the supplementation with bioactive ingredients induced fatty acid oxidation and cholesterol catabolism, and decreased adipogenesis and inflammation. These results reveal molecular mechanisms underlying the beneficial effects of bioactive ingredient supplementation in an obese pig model. administration of Bifidobacterium breve B-3 modified the hepatic expression of genes related to lipid metabolism and response to stress 4 . A reduction in body fat has been also observed in healthy pre-obese individuals receiving Bifidobacterium breve B-3, but no significant improvement of blood parameters was found 5 . In partial agreement, studies with rodent models of obesity have demonstrated the anti-obesity effect of n-3 polyunsaturated fatty acids (PUFA). Reduction of fat mass was predominantly observed in mice fed a HFD and supplemented with n-3 PUFA (reviewed in 6 ). However, the effects of n-3 PUFA in human obesity remain inconclusive. On the other hand, rice proteins and their hydrolysates added to high fat and/or high cholesterol diets have shown to have anti-obesity and hypocholesterolemic effects through the effective modulation of cholesterol and triglyceride metabolism, and the activity of hepatic genes related to lipid metabolism 7,8 .Overall, these experimental evidences reinforce the relevance of using bioactive dietetic supplements to prevent and treat obesity. However, as most of these studies were performed in rodent models, the underlying biological mechanisms determining anti-obesity effects are difficult to translate into humans, due to the vast differences between these species at the physiological and metabolic level 9 . In contrast, pigs are excellent models for human obesity and its comorbidities, given their similarity in terms of anatomy, physiology, metabolism, and genetics 9-11 .To date, a limited number of pig models for childhood obesity have been developed by short term (≤ 12 wk.) dietary interven...

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Section: Discussionsupporting

confidence: 85%

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity

Ballester

Quintanilla

Ortega

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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“…Inflammation is well-known throughout the process of atherosclerotic plaque formation, destabilization, and rupture ( 24 ). TSG-6 contributes to prevent atherosclerosis by suppressing the inflammatory responses and oxidized LDL-induced foam cell formation and the migration and proliferation of vascular smooth muscle cells ( 25 ). Additionally, both animal and human studies have shown the expression of TSG-6 in atherosclerotic lesions, for instance, its localization in rat neointima after arterial injury, rabbit carotid atherosclerotic plaques, and human atherosclerotic fibrous cap ( 7 , 8 , 26 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

Plasma Concentration of Tumor Necrosis Factor-Stimulated Gene-6 as a Novel Diagnostic and 3-Month Prognostic Indicator in Non-Cardioembolic Acute Ischemic Stroke

Yang

Meng

et al. 2022

Front. Immunol.

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BackgroundTumor necrosis factor-stimulated gene-6 (TSG-6) is a multifunctional, anti-inflammatory, and protective protein, while the association between TSG-6 and acute ischemic stroke (AIS) remains unclear in humans. This study aims to investigate the potential diagnostic and short-term prognosis predictive values of TSG-6 in non-cardioembolic AIS.MethodsA total of 134 non-cardioembolic AIS patients within 24 h after AIS onset and 40 control subjects were recruited. Using an AIS dataset from the Gene Expression Omnibus database and setting the median expression level of TNFAIP6 as the cutoff point, data were divided into TNFAIP6-high and TNFAIP6-low expression groups. Differently expressed genes (DEGs) were extracted to perform gene enrichment analysis and protein–protein interaction (PPI) network. Baseline data were analyzed in a four-group comparison plotted as plasma TSG-6 concentration median and 25th/75th percentiles. The correlative factors of 3-month outcome were evaluated by logistic regression. TSG-6 concentrations and TSG-6-to-interleukin-8 ratios were compared in a block design. A receiver-operating characteristic curve was used to analyze the detective value of TSG-6 and 3-month prognosis predictive values of TSG-6 and TSG-6-to-interleukin-8 ratio.ResultsNon-cardioembolic AIS patients had significantly higher plasma TSG-6 levels than control subjects (P < 0.0001). The large-artery atherosclerosis group had significantly higher TSG-6 levels than the small-artery occlusion group (P = 0.0184). Seven hundred and eighty-two DEGs might be both AIS-related and TNFAIP6-correlated genes, and 17 targets were deemed AIS-related being closely relevant to TNFAIP6. Interleukin-8 was selected for further study. The National Institutes of Health Stroke Scale and the Acute Stroke Registry and Analysis of Lausanne scores at admission, lesion volume, neutrophil count, neutrophil-to-lymphocyte ratio, and interleukin-8 level were positively correlated with TSG-6 level, respectively (P < 0.0001). The unfavorable outcome group had meaningfully higher TSG-6 levels (P < 0.0001) and lower TSG-6-to-interleukin-8 ratios (P < 0.0001) than the favorable outcome group. After adjusting for confounding variables, elevated TSG-6 levels remained independently associated with 3-month poor prognosis of non-cardioembolic AIS (P = 0.017). In non-cardioembolic AIS, the cutoff values of TSG-6 concentration for detection and 3-month prognosis prediction and the TSG-6-to-interleukin-8 ratio for the 3-month prognosis prediction were 8.13 ng/ml [AUC, 0.774 (0.686–0.861); P < 0.0001], 10.21 ng/ml [AUC, 0.795 (0.702–0.887); P < 0.0001], and 1.505 [AUC, 0.873 (0.795–0.951); P < 0.0001].ConclusionsPlasma TSG-6 concentration was a novel indicator for non-cardioembolic AIS diagnosis and 3-month prognosis. Elevated TSG-6-to-interleukin-8 ratio might suggest a 3-month favorable outcome.

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“…TSG-6 (Tumor Necrosis Factor, Alpha-Stimulated Gene-6 Protein) TSG-6 is a secreted 35-kDa glycoprotein that contains multiple adjacent functional domains. TSG-6 is not a constitutively expressed protein but is rapidly upregulated in both inflammatory cells and tissue cells upon exposure to inflammatory mediators, including IL-1b, IFN-g, TNF-a, LPS, and PGE2 (65). Besides, it can also be induced by many growth factors including FGF, EGF, and TGF-b.…”

Section: Potential Reagentsmentioning

confidence: 99%

The Roles of Inflammation in Keloid and Hypertrophic Scars

et al. 2020

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The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments.

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Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

Cited by 16 publications

References 54 publications

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity

Plasma Concentration of Tumor Necrosis Factor-Stimulated Gene-6 as a Novel Diagnostic and 3-Month Prognostic Indicator in Non-Cardioembolic Acute Ischemic Stroke

The Roles of Inflammation in Keloid and Hypertrophic Scars

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