Inhibition of miR-155 attenuates abdominal aortic aneurysm in mice by regulating macrophage-mediated inflammation

Zhang, Zhidong; Liang, Keke; Zou, Gangqiang; Chen, Xiaosan; Shu, Shi; Wang, Guoquan; Zhang, Kewei; Li, Kun; Zhai, Shengli

doi:10.1042/bsr20171432

Cited by 31 publications

(21 citation statements)

References 56 publications

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“…Studies have shown that miR-155 plays a crucial role in rheumatoid arthritis and osteoarthritis (23). Inhibition of miR-155 attenuated the development of an abdominal aortic aneurysm by regulating macrophage inflammation (24). The paracrine activity of miR-155-enriched exosomes regulated fibroblast proliferation and inflammation in cardiac injury (22).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR‑155‑5p attenuates the valvular damage induced by rheumatic heart disease

Chen

Wen

et al. 2019

Int J Mol Med

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Autoimmunity is involved in the valvular damage caused by rheumatic heart disease (RHd). Increased evidence has linked microRNAs (miRNAs/miRs) to autoimmune disease. Signal transducer and activator of transcription 3 (STAT3) and sphingosine-1-phosphate receptor 1 (S1PR1) and suppressor of cytokine signaling 1 (SOcS1) have been widely studied for their roles in autoimmunity and inflammation. Thus, the current study aims to investigate the role played by miR-155-5p in RHd-induced valvular damage via the S1PR1, SOcS1/STAT3 and interleukin (IL)-6/STAT3 signaling pathways. An RHd rat model was induced by inactivated Group A streptococci and complete Freund's adjuvant. A recombinant adeno-associated virus (AAV-miR155-inhibitor) was used to inhibit the expression of miR-155-5p in the heart. Inflammation and fibrosis were assessed by hematoxylin and eosin staining and Sirius red staining. The expression of miR-155-5p in valvular tissues and serum exosomes was detected by reverse transcription-quantitative PcR. S1PR1, SOcS1, STAT3, phosphorylated STAT3, IL-6 and IL-17 protein expression was detected by western blotting and immunohistochemistry. The relationships between miR-155-5p and S1PR1 and SOcS1 were detected by dual luciferase assays. cytokine concentrations were measured by ELISA. The expression of miR-155-5p in valve tissues and serum exosomes was increased along with decreased S1PR1 and activated SOcS1/STAT3 signaling in the RHd model. The expression of IL-6 and IL-17 was increased in the valves and the serum. dual luciferase assays showed that miR-155-5p directly targeted S1PR1 and SOcS1. Inhibition of valvular miR-155-5p through AAV pretreatment increased S1PR1 expression and inhibited activation of the SOcS1/STAT3 signal pathway as a result of attenuated valvular inflammation and fibrosis as well as a decrease in IL-6 and IL-17 in the valves and serum. These results suggest that inhibition of miR-155-5p can reduce RHd-induced valvular damage via the S1PR1, SOcS1/STAT3 and IL-6/STAT3 signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Inhibition of miR‑155‑5p attenuates the valvular damage induced by rheumatic heart disease

Chen

Wen

et al. 2019

Int J Mol Med

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“…8 Additionally, miR-155 has been recently reported to regulate macrophage-mediated inflammation during atherogenesis. 9 In general, miRNAs are thought to act within the cells where they are generated. However, recent studies have suggested that miRNAs are present in circulating exosomes.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Circulating Exosome-Mediated Delivery of miR-155 as a Novel Mechanism for Acute Lung Inflammation

et al. 2019

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Emerging evidence has revealed that excessive activation of macrophages may result in an adverse lung inflammation involved in sepsis-related acute lung injury (ALI). However, it has never been clearly identified whether peripheral circulating serum exosomes participate in the pathogenesis of sepsis-related ALI. Therefore, the purposes of our study were to investigate the effect of serum exosomes on macrophage activation and elucidate a novel mechanism underlying sepsisrelated ALI. Here we found that exosomes were abundant in the peripheral blood from ALI mice and selectively loaded microRNAs (miRNAs), such as miR-155. In vivo experiments revealed that intravenous injection of serum exosomes harvested from ALI mice, but not control mice, increased the number of M1 macrophages in the lung, and it caused lung inflammation in naive mice. In vitro, we demonstrated that serum exosomes from ALI mice delivered miR-155 to macrophages, stimulated nuclear factor kB (NF-kB) activation, and induced the production of tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6. Furthermore, we also showed that serum exosome-derived miR-155 promoted macrophage proliferation and inflammation by targeting SHIP1 and SOCS1, respectively. Collectively, our data suggest the important role of circulating exosomes secreted into peripheral blood as a key mediator of septic lung injury via exosome-shuttling miR-155.

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“…A significant upregulation of miR-155-5p was identified in various cardiovascular diseases including AAA and was linked to the inflammatory response in aortic wall. It was demonstrated that expression of miR-155 correlated with inflammatory macrophage response and extracellular matrix destruction in AAA model mice [33]. On the contrary, we identified miR-155-5p as the most strongly downregulated miRNA in TAA tissue.…”

Section: Discussionmentioning

confidence: 56%

“…The distinct disease entities at the molecular level may be regulated by specific, at least partially, miRNA networks. Previous studies have demonstrated that miRNAs play key roles during the formation of AAA by dysregulating VSMC homeostasis and extracellular matrix (ECM) composition or inducing vascular inflammatory response [33,34]. However, a global high-throughput miRNA-sequencing data of TAA tissue and plasma was still missing, despite some experimental data obtained by miRNA microarrays [19,20,35].…”

Section: Discussionmentioning

confidence: 99%

Tissue-Specific miRNAs Regulate the Development of Thoracic Aortic Aneurysm: The Emerging Role of KLF4 Network

Gasiulė

Stankevičius

Patamsytė

et al. 2019

JCM

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MicroRNAs (miRNAs) are critical regulators of the functional pathways involved in the pathogenesis of cardiovascular diseases. Understanding of the disease-associated alterations in tissue and plasma will elucidate the roles of miRNA in modulation of gene expression throughout development of sporadic non-syndromic ascending thoracic aortic aneurysm (TAA). This will allow one to propose relevant biomarkers for diagnosis or new therapeutic targets for the treatment. The high-throughput sequencing revealed 20 and 17 TAA-specific miRNAs in tissue and plasma samples, respectively. qRT-PCR analysis in extended cohort revealed sex-related differences in miR-10a-5p, miR-126-3p, miR-155-5p and miR-148a-3p expression, which were the most significantly dysregulated in TAA tissues of male patients. Unexpectedly, the set of aneurysm-related miRNAs in TAA plasma did not resemble the tissue signature suggesting more complex organism response to the disease. Three of TAA-specific plasma miRNAs were found to be restored to normal level after aortic surgery, further signifying their relationship to the pathology. The panel of two plasma miRNAs, miR-122-3p, and miR-483-3p, could serve as a potential biomarker set (AUC = 0.84) for the ascending TAA. The miRNA-target enrichment analysis exposed TGF-β signaling pathway as sturdily affected by abnormally expressed miRNAs in the TAA tissue. Nearly half of TAA-specific miRNAs potentially regulate a key component in TGF-β signaling: TGF-β receptors, SMADs and KLF4. Indeed, using immunohistochemistry analysis we detected increased KLF4 expression in 27% of TAA cells compared to 10% of non-TAA cells. In addition, qRT-PCR demonstrated a significant upregulation of ALK1 mRNA expression in TAA tissues. Overall, these observations indicate that the alterations in miRNA expression are sex-dependent and play an essential role in TAA via TGF-β signaling.

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Inhibition of miR-155 attenuates abdominal aortic aneurysm in mice by regulating macrophage-mediated inflammation

Cited by 31 publications

References 56 publications

Inhibition of miR‑155‑5p attenuates the valvular damage induced by rheumatic heart disease

Inhibition of miR‑155‑5p attenuates the valvular damage induced by rheumatic heart disease

Peripheral Circulating Exosome-Mediated Delivery of miR-155 as a Novel Mechanism for Acute Lung Inflammation

Tissue-Specific miRNAs Regulate the Development of Thoracic Aortic Aneurysm: The Emerging Role of KLF4 Network

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