Acute lung injury (ALI) is one of the most prevalent respiratory syndromes of excessive inflammatory reaction during lung infection. Candida albicans (C. albicans) infection is among the leading causes of ALI. MicroRNAs (miRNAs) regulate the expression of target mRNAs, including those involved in inflammatory processes, by binding to the 3′UTR. To date, the roles of miRNAs in C. albicans-induced ALI remain unclear. In this study, we investigated the role of miR-384-5p in C. albicans-induced ALI and its underlying molecular mechanism. RT-PCR, Western blot, ELISA, Myeloperoxidase (MPO) assay, microRNA target analysis, transient transfection, and luciferase reporter assay were utilized. In vivo study was conducted on mouse model. The expression of miR-384-5p was upregulated and positively correlated with inflammatory cytokine production in lung tissues and RAW264.7 and J774A.1 macrophages infected with C. albicans. The miR-384-5p inhibitor alleviated the inflammatory reaction induced by C. albicans. Target prediction analysis revealed that PGC1β was a target of miR-384-5p, which was further validated by the PGC1β 3′-UTR luciferase assay and the inverse correlation between the expression of miR-384-5p and PGC1β in C. albicans-infected ALI tissues and macrophages. Moreover, macrophages transfected with miR-384-5p mimic exhibited reduced levels of PGC1β. The suppression of the expression of PGC1β by C. albicans infection in the macrophages was abrogated by miR-384-5p inhibitor. Then, we demonstrated that PGC1β played an inhibitory role in C. albicans-induced production of inflammatory cytokines. Furthermore, suppression of miR-384-5p in macrophages inhibited the activation of the NF-κB, MAPK, and Akt signaling pathways triggered by C. albicans, but not the STAT3 pathway. These results demonstrate that miR-384-5p contributes to C. albicans-induced ALI at least in part by targeting PGC1β and enhancing the activation of the NF-κB, MAPK, and Akt inflammatory signaling pathways. Thus, targeting miR-384-5p might exert a protective effect on C. albicans-induced ALI.

急性肺损伤（ALI）是肺部感染过程中过度炎症反应最常见的呼吸综合征之一。白色念珠菌( C. albicans ) 感染是 ALI 的主要原因之一。MicroRNA (miRNA) 通过与 3'UTR 结合来调节靶标 mRNA 的表达，包括那些参与炎症过程的 mRNA。迄今为止，miRNA 在白色念珠菌诱导的 ALI 中的作用仍不清楚。在本研究中，我们研究了 miR-384-5p 在白色念珠菌诱导的 ALI中的作用及其潜在分子机制。采用 RT-PCR、Western blot、ELISA、髓过氧化物酶 (MPO) 测定、microRNA 靶点分析、瞬时转染和荧光素酶报告基因测定。在小鼠模型上进行了体内研究。感染白色念珠菌的肺组织以及RAW264.7和J774A.1巨噬细胞中miR-384-5p的表达上调，并与炎症细胞因子的产生呈正相关。miR-384-5p抑制剂减轻了白色念珠菌引起的炎症反应。靶标预测分析显示PGC1β是miR-384-5p的靶标，通过PGC1β 3'-UTR荧光素酶测定进一步验证了这一点，并且白色念珠菌感染中miR-384-5p和PGC1β表达之间的负相关性ALI 组织和巨噬细胞。此外，转染miR-384-5p模拟物的巨噬细胞表现出PGC1β水平降低。miR-384-5p 抑制剂消除了巨噬细胞中白色念珠菌感染对 PGC1β 表达的抑制。然后，我们证明 PGC1β 在白色念珠菌诱导的炎症细胞因子的产生中发挥抑制作用。此外，抑制巨噬细胞中的 miR-384-5p 会抑制白色念珠菌触发的 NF-κB、MAPK 和 Akt 信号通路的激活，但不会抑制 STAT3 通路的激活。这些结果表明，miR-384-5p至少部分通过靶向 PGC1β 并增强 NF-κB、MAPK 和 Akt 炎症信号通路的激活来促进白色念珠菌诱导的 ALI。因此，靶向 miR-384-5p 可能对白色念珠菌诱导的 ALI产生保护作用。