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OVA 诱导的气道重塑模型小鼠差异表达 microRNAs 的分析。

Analysis of Differentially Expressed MicroRNAs in OVA-induced Airway Remodeling Model Mice.

机构信息

Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, Jilin, China.

Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Respiratory Medicine, Affiliated Hospital of Yanbian University, Yanji, Jilin, China.

出版信息

Iran J Allergy Asthma Immunol. 2022 Oct 26;21(5):524-536. doi: 10.18502/ijaai.v21i5.11040.

DOI:10.18502/ijaai.v21i5.11040
PMID:36341561
Abstract

MicroRNAs (miRNAs) can participate in airway remodeling by regulating immune molecule expression. Here, we aimed to identify the differential miRNAs involved in airway remodeling. Airway remodeling was induced by ovalbumin in female BALB/C mice. The differentially expressed miRNAs were screened with microarray. GO (Gene Ontology) and KEGG enrichment analysis was performed. The miRNA target gene network and miRNA target pathway network were constructed. Verification with real-time PCR and Western blot was performed. We identified 63 differentially expressed miRNAs (50 up-regulated and 13 down-regulated) in the lungs of ovalbumin-induced airway remodeling mice. Real-time PCR confirmed that 3 miRNAs (mmu-miR-1931, mmu-miR-712-5p, and mmu-miR-770-5p) were significantly up-regulated, and 4 miRNAs (mmu-miR-128-3p, mmu-miR-182-5p, mmu-miR-130b-3p, and mmu-miR-20b-5p) were significantly down-regulated. The miRNA target gene network analysis identified key mRNAs in the airway remodeling, such as Tnrc6b (trinucleotide repeat containing adaptor 6B), Sesn3 (sestrin 3), Baz2a (bromodomain adjacent to zinc finger domain 2a), and Cux1 (cut like homeobox 1). The miRNA target pathway network showed that the signal pathways such as MAPK (mitogen-activated protein kinase), PI3K/Akt (phosphoinositide 3-Kinase/protein kinase B), p53 (protein 53), and mTOR (mammalian target of rapamycin) were closely related to airway remodeling in asthma. Collectively, differential miRNAs involved in airway remodeling (such as mmu-miR-1931, mmu-miR-712-5p, mmu-miR-770-5p, mmu-miR-128-3p mmu-miR-182-5p, and mmu-miR-130b-3p) as well as their target genes (such as Tnrc6b, Sesn3, Baz2a, and Cux1) and pathways (such as MAPK, PI3K/Akt, p53, mTOR pathways) have been identified. Our findings may help to further understand the pathogenesis of airway remodeling.

摘要

微小 RNA(miRNA)可以通过调节免疫分子的表达参与气道重塑。在这里,我们旨在确定参与气道重塑的差异表达 miRNA。用卵清蛋白诱导雌性 BALB/C 小鼠气道重塑。采用微阵列筛选差异表达的 miRNA。进行 GO(基因本体论)和 KEGG 富集分析。构建 miRNA 靶基因网络和 miRNA 靶途径网络。采用实时 PCR 和 Western blot 进行验证。我们在卵清蛋白诱导的气道重塑小鼠的肺部中鉴定出 63 个差异表达的 miRNA(50 个上调和 13 个下调)。实时 PCR 证实 3 个 miRNA(mmu-miR-1931、mmu-miR-712-5p 和 mmu-miR-770-5p)显著上调,4 个 miRNA(mmu-miR-128-3p、mmu-miR-182-5p、mmu-miR-130b-3p 和 mmu-miR-20b-5p)显著下调。miRNA 靶基因网络分析确定了气道重塑中的关键 mRNAs,如 Tnrc6b(三核苷酸重复包含接头 6B)、Sesn3( sestrin 3)、Baz2a(溴结构域相邻锌指结构域 2a)和 Cux1(cut like homeobox 1)。miRNA 靶途径网络显示,MAPK(丝裂原激活蛋白激酶)、PI3K/Akt(磷酸肌醇 3-激酶/蛋白激酶 B)、p53(蛋白 53)和 mTOR(哺乳动物雷帕霉素靶蛋白)等信号通路与哮喘中的气道重塑密切相关。总之,鉴定出参与气道重塑的差异表达 miRNA(如 mmu-miR-1931、mmu-miR-712-5p、mmu-miR-770-5p、mmu-miR-128-3p、mmu-miR-182-5p 和 mmu-miR-130b-3p)及其靶基因(如 Tnrc6b、Sesn3、Baz2a 和 Cux1)和途径(如 MAPK、PI3K/Akt、p53、mTOR 途径)。我们的发现可能有助于进一步了解气道重塑的发病机制。

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