Adipogenic miR-27a in adipose tissue upregulates macrophage activation via inhibiting PPARγ of insulin resistance induced by high-fat diet-associated obesity

Fan, Yao; Yu, Yang; Feng, Linjing; Li, Junnan; Zhang, Meishuang; Lan, Xiaoxin; Yan, Xin; Liu, Yilun; Guan, Fengying; Zhang, Ming; Chen, Li

doi:10.1016/j.yexcr.2017.03.060

Cited by 84 publications

(65 citation statements)

References 34 publications

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“…MiR‐20 has previously been associated with cyclin D1 and has been shown to be associated with vascular endothelial growth factor, a cytokine, via activation of Akt signaling . MiR‐27a‐3p has been shown to promote cell proliferation and invasion possibly through its association with the cytokine TRAIL (TNF‐related apoptosis‐inducing ligand) or through its effects on insulin . IL6R differential expression also was inversely associated with miR‐21‐5p suggesting a direct association between this mRNA and miRNA.…”

Section: Discussionmentioning

confidence: 99%

The PI3K/AKT signaling pathway: Associations of miRNAs with dysregulated gene expression in colorectal cancer

Slattery

Mullany

Sakoda

et al. 2017

Molecular Carcinogenesis

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The PI3K/AKT-signaling pathway is one of the most frequently activated signal-transduction pathways in cancer. We examined how dysregulated gene expression is associated with miRNA expression in this pathway in colorectal cancer (CRC). We used data from 217 CRC cases to evaluate differential pathway gene expression between paired carcinoma and normal mucosa and identify miRNAs that are associated with these genes. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were analyzed. We focused on genes most associated with CRC (fold change (FC) of >1.5 or <0.67) that were statistically significant after adjustment for multiple comparisons. Of the 304 genes evaluated, 76 had a FC of <0.67 and 57 had a FC of >1.50; 47 of these genes were associated with miRNA differential expression. There were 145 mRNA:miRNA seed-region matches of which 26 were inversely associated suggesting a greater likelihood of a direct association. Most miRNA:mRNA associations were with factors that stimulated the pathway. For instance, both IL6R and PDGFRA had inverse seed-region matches with seven miRNAs, suggesting that these miRNAs have a direct effect on these genes and may be key elements in activation of the pathway. Other miRNA:mRNA associations with similar impact on the pathway were miR-203a with ITGA4, miR-6071 with ITGAV, and miR-375 with THBS2, all genes involved in extracellular matrix function that activate PI3Ks. Gene expression in the PI3K/Akt-signaling pathway is dysregulated in CRC. MiRNAs were associated with many of these dysregulated genes either directly or in an indirect manner.

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Section: Discussionmentioning

confidence: 99%

The PI3K/AKT signaling pathway: Associations of miRNAs with dysregulated gene expression in colorectal cancer

Slattery

Mullany

Sakoda

et al. 2017

Molecular Carcinogenesis

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“…Some of the mechanisms are based solely on data from animals or in vitro studies and thus are not easily applicable for a general evaluation of the importance of ATMs in a human setting. Recent studies from both mice and humans have demonstrated that AT is a crucial source of circulating exosomal miRNAs that have systemic effects on metabolism as well as on specific tissues, providing a novel pathway of cell‐cell crosstalk in regulating ATM function . Furthermore, there are broader areas that need to be understood, including the role of epigenetic regulation and post‐translational modifications on the regulation of the metabolism and inflammation of ATMs and whether targeting ATM polarization is a promising strategy to suppress the progress of some chronic metabolic diseases, such as insulin resistance, CVDs, and cancers.…”

Section: Resultsmentioning

confidence: 99%

Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases

Zhu

Chen

et al. 2018

Diabetes Metabolism Res

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The accumulation and pro-inflammatory polarization of immune cells, mainly macrophages, in adipose tissue (AT) are considered crucial factors for obesity-induced chronic inflammatory diseases. In this review, we highlighted the role of adipose tissue macrophage (ATM) polarization on AT function in the obese state and the effect of the micro-environment and intracellular metabolism on the dynamic switch of ATMs into their pro-inflammatory or anti-inflammatory phenotypes, which may have distinct influences on obesity-related chronic inflammatory diseases. Obesity-associated metabolic dysfunctions, including those of glucose, fatty acid, cholesterol, and other nutrient substrates such as vitamin D and iron in AT, promote the pro-inflammatory polarization of ATMs and AT inflammation via regulating the interaction between ATMs and adipocytes and intracellular metabolic pathways, including glycolysis, fatty acid oxidation, and reverse cholesterol transportation. Focusing on the regulation of ATM metabolism will provide a novel target for the treatment of obesity-related chronic inflammatory diseases, including insulin resistance, cardiovascular diseases, and cancers.

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“…It has been shown that miRNAs in humans are involved in, among other things, the regulation of processes such as hematopoietic stem cell differentiation, neurogenesis, embryogenesis, angiogenesis, insulin secretion, differentiation of mononuclear cells and the formation and activity of immune system cells [65][66][67][68]. Moreover, their significance in such conditions as inflammation, cancers, autoimmune diseases and cardiovascular diseases has been confirmed [64,[69][70][71][72][73][74][75][76][77][78][79][80][81][82]. The usefulness of miRNAs as biomarkers in cardiovascular diseases results from their participation in pathophysiological processes related to cardiovascular diseases as well as their stability in blood and urine [83].…”

Section: The Participation Of Micro-rna In Inflammation In Hfmentioning

confidence: 99%

Various aspects of inflammation in heart failure

et al. 2019

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Despite significant advances in the prevention and treatment of heart failure (HF), the prognosis in patients who have been hospitalised on at least one occasion due to exacerbation of HF is still poor. Therefore, a better understanding of the underlying pathophysiological mechanisms of HF is crucial in order to achieve better results in the treatment of this clinical syndrome. One of the areas that, for years, has aroused the interest of researchers is the activation of the immune system and the elevated levels of biomarkers of inflammation in patients with both ischaemic and non-ischaemic HF. Additionally, it is intriguing that the level of circulating pro-inflammatory biomarkers correlates with the severity of the disease and prognosis in this group of patients. Unfortunately, clinical trials aimed at assessing interventions to modulate the inflammatory response in HF have been disappointing, and the modulation of the inflammatory response has had either no effect or even a negative effect on the HF prognosis. The article presents a summary of current knowledge on the role of immune system activation and inflammation in the pathogenesis of HF. Understanding the immunological mechanisms pathogenetically associated with left ventricular remodelling and progression of HF may open up new therapeutic possibilities for HF.

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Adipogenic miR-27a in adipose tissue upregulates macrophage activation via inhibiting PPARγ of insulin resistance induced by high-fat diet-associated obesity

Cited by 84 publications

References 34 publications

The PI3K/AKT signaling pathway: Associations of miRNAs with dysregulated gene expression in colorectal cancer

The PI3K/AKT signaling pathway: Associations of miRNAs with dysregulated gene expression in colorectal cancer

Micro‐environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases

Various aspects of inflammation in heart failure

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