Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders

Yao, Zhenhua; Chen, Wenbin; Shao, Shanshan; Ma, Shizhan; Yang, Chengzhe; Li, Meng-zhu; Zhao, Jiajun; Gao, Ling

doi:10.1631/jzus.b1600490

Cited by 43 publications

(29 citation statements)

References 101 publications

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“…Exosomes are released by most of the cells into the circulation and bodily fluids display different protein and RNA contents in healthy subjects and patients with different diseases, which can be measured as potential diagnostic markers [ 198 , 199 ]. Several studies have examined circulating exosomes in human obesity and metabolic syndrome [ 200 , 201 , 202 , 203 ]. Obesity and other associated metabolic disorders induce increased secretion of vesicles incorporating specific RNAs and proteins as observed in both rodents and humans [ 204 , 205 ].…”

Section: Exosomes and Metabolic Dysfunctionmentioning

confidence: 99%

Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction

Kheirandish‐Gozal

Gozal

2018

IJMS

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Obstructive sleep apnea (OSA) is a highly prevalent worldwide public health problem that is characterized by repetitive upper airway collapse leading to intermittent hypoxia, pronounced negative intrathoracic pressures, and recurrent arousals resulting in sleep fragmentation. Obesity is a major risk factor of OSA and both of these two closely intertwined conditions result in increased sympathetic activity, oxidative stress, and chronic low-grade inflammation, which ultimately contribute, among other morbidities, to metabolic dysfunction, as reflected by visceral white adipose tissue (VWAT) insulin resistance (IR). Circulating extracellular vesicles (EVs), including exosomes, are released by most cell types and their cargos vary greatly and reflect underlying changes in cellular homeostasis. Thus, exosomes can provide insights into how cells and systems cope with physiological perturbations by virtue of the identity and abundance of miRNAs, mRNAs, proteins, and lipids that are packaged in the EVs cargo, and are secreted from the cells into bodily fluids under normal as well as diseased states. Accordingly, exosomes represent a novel pathway via which a cohort of biomolecules can travel long distances and result in the modulation of gene expression in selected and targeted recipient cells. For example, exosomes secreted from macrophages play a critical role in innate immunity and also initiate the adaptive immune response within specific metabolic tissues such as VWAT. Under normal conditions, phagocyte-derived exosomes represent a large portion of circulating EVs in blood, and carry a protective signature against IR that is altered when secreting cells are exposed to altered physiological conditions such as those elicited by OSA, leading to emergence of IR within VWAT compartment. Consequently, increased understanding of exosome biogenesis and biology should lead to development of new diagnostic biomarker assays and personalized therapeutic approaches. Here, the evidence on the major biological functions of macrophages and exosomes as pathophysiological effectors of OSA-induced metabolic dysfunction is discussed.

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Section: Exosomes and Metabolic Dysfunctionmentioning

confidence: 99%

Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction

Kheirandish‐Gozal

Gozal

2018

IJMS

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“…Thus, circulating miRNAs have been widely used as biomarkers in different types of human diseases such as liver diseases, tumors, diabetes, heart failure, coronary diseases and stable angina. [37][38][39][40] The current research on the relationship between microRNAs and pulmonary embolism had been performed Figure 2 Receiver-operating characteristic (ROC) curve analysis of serum miR-1233, miR-134, plasma D-dimer to discriminate AECOPD+APE patients from AECOPD controls. (A) The analysis showed that the receiver operating characteristic (ROC) area under the curve (AUC) for miR-1233 was 0.884 (95% CI 0.79-0.978)(P<0.05), the AUC for miR-134 was 0.931 (95% CI 0.863-0.999)(P<0.05); (B) the AUC for D-dimer was 0.628 (95% CI 0.447-0.809), the AUC for age-adjusted plasma D-dimer was 0.705 (95% CI 0.525-0.885), and the AUC for Wells score was 0.577 (95% CI 0.389-0.765).…”

Section: Discussionmentioning

confidence: 99%

<p>The Predictive Value of microRNA-134 and microRNA-1233 for the Early Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Pulmonary Embolism</p>

Peng¹,

Han²,

Li³

et al. 2020

COPD

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Background: The differential diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with acute pulmonary embolism (APE) complications are difficult because of the variability of clinical presentations and the shortage of an unfailing screening biomarkers or instruments. Objective: Aimed to detect and compare the expression of serum microRNAs (miR-1233, miR-134) in AECOPD patients complicated with APE. Patients/Methods: Blood samples were collected from 52 AECOPD patients (13 patients with APE complications, 39 patients without APE) and 10 patients with stable COPD. Serum miRNAs expression was detected with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The levels of plasma D-dimers were determined by detection with an enzyme-linked immunosorbent assay (ELISA). The receiver-operator characteristic (ROC) curve was used for evaluating the diagnostic accuracy of the studied miRNAs. Results: According to the Wells score, 42 of the 52 AECOPD patients were unlikely to have APE (≤4 points), whereas the remaining 10 (>4 points) were likely to have APE. There were 4 cases (4/13 30.8%) in the AECOPD combined with APE group with a Wells score of >4 points. The expression levels of miR-1233 and miR-134 in the serum were considerably upregulated in the AECOPD+APE group compared with the AECOPD group and the stable COPD group (P<0.05). The areas under the curve (AUCs) for miR-134 and miR-1233 were, respectively, 0.931 (95% CI 0.863-0.999) (P<0.05) and 0.884 (95% CI 0.79-0.978) (P<0.05) and were higher compared with the AUC for D-dimer of 0.628 (95% CI 0.447-0.809), the AUC for age-adjusted D-dimer of 0.705 (95% CI 0.525-0.885) and the AUC for Wells score of 0.577 (95% CI 0.389-0.765). Conclusion: Our study indicated that serum miR-1233 and miR-134 have high clinical value in the early diagnosis of AECOPD patients combined with APE, or could be used as potential biomarkers for clinical identification of AECOPD with or without APE complication.

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“…In addition, detection of exosomal protein; both CD9 and CD63 the well-known exosomal markers, and their expression were analyzed by Western blotting. Recent studies have detected more and more exosome associated miRNAs associated with different kinds of chronic diseases, especially metabolic disorders such as diabetes mellitus, fatty liver, obesity, and atherosclerosis [47].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Circulating Exosomal MicroRNAs and Its Role as Biomarkers for Metabolic Syndrome

El-Dawy

Ali

Abdo

2019

Zagazig Veterinary Journal

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Exosomal microRNAs (EXO-miRNAs) attract major importance as prospective diagnostic biomarkers for metabolic syndrome (MS). The intent of our trials was to characterize the serum exosomes, exosomal miRNA and their target genes to identify those that were altered in relation to the different conditions of metabolic syndrome (Type II diabetes mellitus, high-fat-induced obesity and its related disorders) with different forms of treatment to evaluate their use as diagnostic and treatment biomarkers. Eighty male adult albino rats were used in this experiment, 10 served as normal control group and other 70 divided into 7 different groups; the first received high fat high fructose (HFHF) diet for 4 weeks, second received HFHF diet and confirmed to be diabetic and the other five groups are diabetics and treated for another 4 weeks with Okra extract, Gum Arabic, Dapagliflozin, combination of Dapagliflozin& okra Extract and combination of Dapagliflozin& Gum Arabic, respectively.. Our results explained that, the expression levels of miR-122, fatty acid synthase-1 (FAS-1) and Sterol response elementary binding protein-1 (SREBP-1) were significantly higher in the hepatic tissue of metabolic syndrome model groups than that of control and significantly down-regulated after different treatments but still higher than that of control group while carnitine palmitoyltransferase-1(CPT-1) was significantly decreased in the same groups. Also the expression levels of miR-31 was significantly higher in adipose tissue of metabolic syndrome model groups than that of control and significantly down-regulated after different treatments but still higher than that of control group while Leptin gene (Ob), Phosphoinositide-3-kinase, class 2, alpha-polypeptide (PIK3C2A) and Peroxisome proliferator-activated receptor-γ (PPAR-γ) were significantly decreased in the same groups.It was concluded that exosomal miRNA signatures are parallel with pathological consequences of metabolic syndrome sufferers as well as numerous miRNAs display potential biomarkers for non-invasive diagnosis of the metabolic changes.

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Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders

Cited by 43 publications

References 101 publications

Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction

Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction

<p>The Predictive Value of microRNA-134 and microRNA-1233 for the Early Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Pulmonary Embolism</p>

Characterization of Circulating Exosomal MicroRNAs and Its Role as Biomarkers for Metabolic Syndrome

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