MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease

Nakaoka, Hideyuki; Hirono, Keiichi; Yamamoto, Seiji; Takasaki, Ichiro; Takahashi, Kei; Kinoshita, Koshi; Takasaki, Asami; Nishida, Naonori; Okabe, Mako; Wang, Ce; Miyao, Nariaki; Saito, Kazuyoshi; Ibuki, Keijiro; Ozawa, Sayaka; Adachi, Yuichi; Ichida, Fukiko

doi:10.1038/s41598-018-19310-4

Cited by 35 publications

(33 citation statements)

References 42 publications

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“…We found that the expression of HMGB1/sRAGE/ NF-κB increased in the acute phase of KD. Notably, in the acute phase of KD, the CAL group exhibited higher levels than the NCAL group, as regards these three indicators [30]. Furthermore, we established a rabbit model of KD.…”

Section: Discussionmentioning

confidence: 96%

Mechanism of HMGB1–RAGE in Kawasaki disease with coronary artery injury

et al. 2020

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Background: Kawasaki disease (KD) is a common, yet unknown etiology disease in Asian countries, which causes acquired heart disease in childhood. It is characterized by an inflammatory acute febrile vasculitis of medium-sized arteries, particularly the coronary arteries. High-mobility group box-1 protein (HMGB1) is a non-histone chromosomalbinding protein present in the nucleus of eukaryotic cells, which contains 215 amino acid residues. Although the cellular signal transduction mechanisms of HMGB1 are currently unclear, the important role of the receptor for advanced glycation end-products (RAGE), the main receptor for HMGB1 has been reported in detail. The purpose of our study was to verify the mechanism and clinical significance of HMGB1-RAGE in coronary artery injury of Kawasaki disease. Methods: 52 blood samples of patients in KD were collected, and the coronary artery Z score was calculated according to the echocardiographic results. The Z score ≥ 2.0 was classified as coronary artery lesions (CAL); otherwise, it was no-coronary artery lesions (NCAL). In addition, the fever group and control group were set. Among them, the fever group were children with fever due to respiratory tract infection at the same time period as KD (heat peak ≥ 38.5 ℃). The normal group were children at a routine physical examination in the outpatient clinic of Nantong University and the physical examination center of the child care insurance, and there were no infectious diseases and heart diseases. The serum levels of HMGB1, RAGE, and NF-κB in each group were detected by ELISA. The animal model of KD was established using the New Zealand young rabbits. We used RT-qPCR/H&E staining/immunohistochemistry/ELISA and western blot to detect the level of HMGB1/RAGE and NF-κB. Results: In this study, we found that the HMGB1/RAGE/NF-κB axis was elevated in the serum of children with KD. In addition, an animal model of KD was subsequently prepared to examine the pathological changes of the coronary arteries. We found that the serum levels of HMGB1/RAGE/NF-κB in rabbits with KD were significantly higher than those of the control group. Moreover, the lumen diameter of the coronary artery was slightly enlarged, and the wall of the tube became thinner and deformed. In addition, the HMGB1/RAGE/NF-κB levels in the coronary artery were higher in the rabbits with KD in the acute phase. Conclusions: On the whole, the findings of this study demonstrate that the expression of HMGB1/RAGE/NF-κB is altered at different stages of KD, suggesting that the HMGB1/RAGE/NF-κB signaling pathway plays an important role in vascular injury in KD. The results of this study may have important implications for the early warning of coronary artery lesions in KD.

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Section: Discussionmentioning

confidence: 96%

Mechanism of HMGB1–RAGE in Kawasaki disease with coronary artery injury

et al. 2020

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“…199 Consistent with whole blood samples, plasma miR-145-5p levels are highly expressed in from patients with KD. 200 Plasma miR-125a-5p levels are also significantly elevated in both of acute and convalescent KD patients compared with controls, suggesting that miR-125a-5p may be potential diagnostic biomarkers for early KD. 201 In the recent study, miR-186 is confirmed to be significantly up-regulated in the serum of patients with KD and in HUVECs stimulated with KD serum, and its serum expression is down-regulated to normal levels in convalescent KD.…”

Section: Kawasaki Diseasementioning

confidence: 95%

The regulatory role of microRNAs in angiogenesis‐related diseases

Sun

Lei

et al. 2018

J Cellular Molecular Medi

119

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MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression at a post‐transcriptional level via either the degradation or translational repression of a target mRNA. They play an irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis‐related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA‐based biomarkers in the diagnosis, treatment and prognosis of angiogenesis‐related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.

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“…Collectively, the studies discussed in this section lead to the conclusion that EMVs have the ability to activate both endothelium and leukocytes, which fortifies migration of leukocytes to the site of inflammation. Recently, Nakaoka et al (154) have put forward important and thought-provoking observations on the proinflammatory mechanism of EMV. First, two unique microRNAs (hsa-miR-145-5p and hsa-miR-320a) were encapsulated in EMVs.…”

Section: Endothelial-derived Microvesicles (Emvs) and Inflammationmentioning

confidence: 99%

Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?

et al. 2018

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The terms microparticles (MPs) and microvesicles (MVs) refer to large extracellular vesicles (EVs) generated from a broad spectrum of cells upon its activation or death by apoptosis. The unique surface antigens of MPs/MVs allow for the identification of their cellular origin as well as its functional characterization. Two basic aspects of MP/MV functions in physiology and pathological conditions are widely considered. Firstly, it has become evident that large EVs have strong procoagulant properties. Secondly, experimental and clinical studies have shown that MPs/MVs play a crucial role in the pathophysiology of inflammation-associated disorders. A cardinal feature of these disorders is an enhanced generation of platelets-, endothelial-, and leukocyte-derived EVs. Nevertheless, anti-inflammatory effects of miscellaneous EV types have also been described, which provided important new insights into the large EV-inflammation axis. Advances in understanding the biology of MPs/MVs have led to the preparation of this review article aimed at discussing the association between large EVs and inflammation, depending on their cellular origin.

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MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease

Cited by 35 publications

References 42 publications

Mechanism of HMGB1–RAGE in Kawasaki disease with coronary artery injury

Mechanism of HMGB1–RAGE in Kawasaki disease with coronary artery injury

The regulatory role of microRNAs in angiogenesis‐related diseases

Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?

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