Department of Pediatrics, College of Medicine, The Pennsylvania State University, Hershey, PA, United States.
Department of Biochemistry and Molecular Biology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States.
Front Immunol. 2022 Jul 1;13:854434. doi: 10.3389/fimmu.2022.854434. eCollection 2022.
Human surfactant protein (SP)-A1 and SP-A2 exhibit differential qualitative and quantitative effects on the alveolar macrophage (AM), including a differential impact on the AM miRNome. Moreover, SP-A rescue (treatment) of SP-A-knockout (KO) infected mice impoves survival. Here, we studied for the first time the role of exogenous SP-A protein treatment on the regulation of lung alveolar cell (LAC) miRNome, the miRNA-RNA targets, and gene expression of SP-A-KO infected mice of both sexes. Toward this, SP-A-KO mice of both sexes were infected with , and half of them were also treated with SP-A2 (1A). After 6 h of infection/SP-A treatment, the expression levels and pathways of LAC miRNAs, genes, and target miRNA-mRNAs were studied in both groups. We found 1) significant differences in the LAC miRNome, genes, and miRNA-mRNA targets in terms of sex, infection, and infection plus SP-A2 (1A) protein rescue; 2) an increase in the majority of miRNA-mRNA targets in both study groups in KO male vs. female mice and involvement of the miRNA-mRNA targets in pathways of inflammation, antiapoptosis, and cell cycle; 3) genes with significant changes to be involved in TP-53, tumor necrosis factor (TNF), and cell cycle signaling nodes; 4) when significant changes in the expression of molecules from all analyses (miRNAs, miRNA-mRNA targets, and genes) were considered, two signaling pathways, the TNF and cell cycle, referred to as "integrated pathways" were shown to be significant; 5) the cell cycle pathway to be present in all comparisons made. Because SP-A could be used therapeutically in pulmonary diseases, it is important to understand the molecules and pathways involved in response to an SP-A acute treatment. The information obtained contributes to this end and may help to gain insight especially in the case of infection.
人表面活性蛋白（SP）-A1 和 SP-A2 对肺泡巨噬细胞（AM）表现出不同的定性和定量影响，包括对 AM 微小 RNA 组的不同影响。此外，SP-A 抢救（治疗）SP-A 敲除（KO）感染的小鼠可提高存活率。在这里，我们首次研究了外源性 SP-A 蛋白治疗对两性 SP-A-KO 感染小鼠肺泡细胞（LAC）微小 RNA 组、微小 RNA-RNA 靶标和基因表达的调节作用。为此，我们用感染了，并且其中一半还用 SP-A2（1A）进行了处理。感染/SP-A 治疗 6 小时后，研究了两组小鼠 LAC 微小 RNA、基因和靶微小 RNA-mRNA 的表达水平和途径。我们发现：1）在性别、感染和感染加 SP-A2（1A）蛋白抢救方面，LAC 微小 RNA 组、基因和微小 RNA-mRNA 靶标存在显著差异；2）在 KO 雄性与雌性小鼠中，大多数微小 RNA-mRNA 靶标在两个研究组中均增加，并且涉及炎症、抗凋亡和细胞周期途径的微小 RNA-mRNA 靶标；3）基因的显著变化涉及 TP-53、肿瘤坏死因子（TNF）和细胞周期信号节点；4）当考虑所有分析（微小 RNA、微小 RNA-mRNA 靶标和基因）中分子表达的显著变化时，两个信号通路，即 TNF 和细胞周期，被认为是显著的；5）细胞周期途径存在于所有比较中。因为 SP-A 可在肺部疾病的治疗中使用，所以了解对 SP-A 急性治疗的反应中涉及的分子和途径很重要。所获得的信息为此做出了贡献，并且可能有助于获得特别在感染情况下的见解。
