原標(biāo)題:通過細(xì)胞外囊泡選擇性釋放miRNAs與屋塵螨引起的氣道炎癥有關(guān)
——來自浙大迪迅
MicroRNAs (miRNAs)可促進(jìn)細(xì)胞間通過胞外囊泡(EVs)進(jìn)行信息傳遞。EVs中miRNAs在過敏性氣道炎癥中的生物學(xué)作用尚不清楚。方法:從小鼠支氣管肺泡灌洗液(BALF)和屋塵螨(HDM)致敏小鼠中分離出呼吸道分泌性EVs (AEVs)。采用miRNA芯片對肺組織中AEVs、miRNA和mRNAs的表達(dá)情況進(jìn)行分析。結(jié)果:與(假藥)對照小鼠相比,戶塵螨暴露小鼠的BALF中AEV增加了8.9倍。HDM暴露導(dǎo)致EVs中139個(gè)miRNAs和肺組織中175個(gè)miRNAs的表達(dá)發(fā)生顯著變化,兩個(gè)樣本中共有54個(gè)共同miRNAs。HDM暴露后,這54個(gè)miRNA在AEVs和肺組織中的表達(dá)變化呈負(fù)相關(guān)性。計(jì)算分析顯示,31個(gè)基因,包括IL-13和IL-5Ra,是AEVs中上調(diào)而HDM暴露后肺組織中下調(diào)的miRNA的可能靶點(diǎn)。使用神經(jīng)磷脂酶抑制劑 GW4869可以減少HDM暴露后BALF中AEV的含量。GW4869可以降低BALFs中Th2細(xì)胞因子和嗜酸性粒細(xì)胞計(jì)數(shù),減少氣道壁和粘膜中嗜酸性粒細(xì)胞的聚集。
結(jié)論:這些結(jié)果表明,在暴露于HDM后, miRNA選擇性的排序進(jìn)入AEVs(包括Th2抑制性miRNA),增加其在氣道的釋放,參與了過敏性氣道炎癥的發(fā)病機(jī)制。
延伸閱讀
Clin Exp Allergy
[IF:6.048]
Selective release of miRNAs via extracellular vesicles is associated with house-dust mite allergen-induced airway inflammation
Abstract:
Summary
Background: MicroRNAs (miRNAs) may facilitate cell-to-cell communication via extracellular vesicles (EVs). The biological roles of miRNAs in EVs on allergic airway inflammation are unclear. Methods: Airway-secreted EVs (AEVs) were isolated from bronchoalveolar lavage fluid (BALF) of control and house-dust mite (HDM) allergen-exposed HDM-sensitized mice. The expression of miRNAs in AEVs or miRNAs and mRNAs in lung tissue was analysed using miRNA microarray. Results: The amount of AEV increased 8.9-fold in BALF from HDM-exposed mice compared with that from sham-control mice. HDM exposure resulted in significant changes in the expression of 139 miRNAs in EVs and 175 miRNAs in lung tissues, with 54 miRNAs being common in both samples. Expression changes of these 54 miRNAs between miRNAs in AEVs and lung tissues after HDM exposure were inversely correlated. Computational analysis revealed that 31 genes, including IL-13 and IL-5Ra, are putative targets of the miRNAs up-regulated in AEVs but downregulated in lung tissues after HDM exposure. The amount of AEV in BALF after HDM exposure was diminished by treatment with the sphingomyelinase inhibitor GW4869. The treatment with GW4869 also decreased Th2 cytokines and eosinophil counts in BALFs and reduced eosinophil accumulation in airway walls and mucosa.
Conclusion: These results indicate that selective sorting of miRNA including Th2 inhibitory miRNAs into AEVs and increase release to the airway after HDM exposure would be involved in the pathogenesis of allergic airway inflammation.
All Authors:
Y. Gon1 | S. Maruoka1 | T. Inoue1 | K. Kuroda2 | K. Yamagishi3 | Y. Kozu1 | S. Shikano1 | K. Soda1 | J. Lotvall € 4,5 | S. Hashimoto1
2018-10-24 Article
創(chuàng)建過敏性疾病的科研、科普知識交流平臺,為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺。