Small RNA Sequencing Reveals Exosomal miRNAs Involved in the Treatment of Asthma by Scorpio and Centipede

Abstract

Asthma is a common respiratory disease with inflammation in the lungs. Exosomes and microRNAs (miRNAs) play crucial role in inflammation, whereas the role of exosomal miRNA in asthma remains unknown. Here, we aimed to identify the key exosomal miRNAs and their underlying mechanisms involved in scorpio and centipede (SC) treatment in asthma. Eighteen mice were randomly divided into three groups: control group, asthma group, and SC treatment group. Effect of SC was assessed by hematoxylin-eosin staining and real-time PCR. Exosomes from asthma and SC treatment groups were analyzed by small RNA-seq. Results revealed SC significantly alleviated the pathogenesis of asthma and suppressed the release of inflammatory cytokines. A total of 328 exosomal miRNAs were differentially expressed between the exosomes from asthma and SC-treated mice, including 118 up- and 210 downregulated in SC-treated mice. The altered exosomal miRNAs were primarily involved in the function of transcription, apoptotic process, and cell adhesion; and pathway of calcium, Wnt, and MAPK signaling. Real-time PCR verified exosomal miR-147 was downregulated, while miR-98-5p and miR-10a-5p were upregulated in SC-treated mice compared to asthma mice. Moreover, the target genes of miR-147-3p, miR-98-5p, and miR-10a-5p were mainly enriched in Wnt and MAPK inflammatory signaling. miR-10a-5p promoted the proliferation of mouse lung epithelial cells and downregulated the expression of Nfat5 and Map2k6. These data suggest SC-induced exosomal miRNAs might mediate the inflammatory signaling and might be involved in the SC treatment in asthma. The exosomal miRNAs might be promising candidates for the treatment of asthma.

Involvement of Circulating Exosomal MicroRNAs in Jian-Pi-Yi-Shen Formula Protection Against Adenine-Induced Chronic Kidney Disease

“…Scorpion and centipede are two anti-inflammatory Chinese medicines, which are used in the therapy of refractory asthma in China. By small RNA sequencing, bronchoalveolar lavage fluid exosomal miR-147-3p, miR-98-5p, and miR-10a-5p were found to be involved in alleviating asthma treated with scorpion and centipede ( Tang et al, 2020 ). Although JPYSF has been used for decades to treat CKD in clinic, the mechanisms are still not fully elucidated.…”

Scorpion and centipede alleviates severe asthma through M2 macrophage-derived exosomal miR-30b-5p

“…The mice were randomly allocated to three groups: sham, SA, and SC. The establishment of the asthma model was performed as reported previously [ 6 ]. During the asthma sensitization, mice in the SA and SC groups were intraperitoneally injected with 0.1 ml of saline solution containing OVA (0.5 mg/mL, Sigma, cat#A5503) and aluminum hydroxide (2 mg/mL, Sigma, V900163).…”

“…It is well-known that SC can improve the level of clinical control, lung function and FeNO in patients with refractory asthma and significantly alleviated the pathogenesis of asthma by suppressing the release of inflammatory cytokines. We previously determined that SC reduced the inflammatory response in asthmatic mice [ 6 ]. Nevertheless, the specific mechanisms of SC therapy remain obscure.…”

“…Exosomal miR-125b may be used as a non-invasive diagnostic indicator for asthma severity with high diagnostic efficacy [ 12 ]. Our previous study found that SC could significantly change miRNA expression in exosomes of bronchoalveolar lavage fluid, thus improving the inflammatory symptoms of mice with asthma [ 6 ]. However, what kinds of exosomes are mainly mediated by SC, and the functions or molecular mechanisms of these exosomes involved in asthma are still unclear.…”

Extracellular Vesicles and Asthma—More Than Just a Co-Existence

“…Taken together, the results of this study suggest a very interesting mechanism in which selective sorting of miRNA, predominantly miRNAs inhibiting type-2 molecules, into airway-secreted EVs and their increased release to the airways after HDM exposure, i.e., removing them from the cells, could be involved in the pathogenesis of AAI [ 100 ]. Interestingly, analysis of BALF exosomes in mice subjected to an OVA-based model of AAI treated with scorpion and centipede demonstrated that BALF exosomal miRNAs might be involved in mediating the anti-asthmatic effects of these traditional Chinese insect medicines [ 101 ].…”