Zhou Rong-Mei, Shi Ze-Hui, Shan Kun, Zhang Shu-Jie, Zhang Yi-Han, Liang Yu, Yan Biao, Zhao Chen
Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.
NHC Key Laboratory of Myopia (Fudan University), Shanghai, China.
Front Genet. 2022 Mar 16;13:823517. doi: 10.3389/fgene.2022.823517. eCollection 2022.
Macrophage polarization is a process that macrophages exert different functions according to surrounding micro-environment. Macrophages commonly exist in two distinct subsets: classically activated M1 macrophages and alternatively activated M2 macrophages. Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated by back-splicing. Thousands of circRNAs were identified in different cells and tissues. Recent studies have revealed that circRNAs play a crucial role in regulating transcriptional and post-transcriptional gene expression. However, the effects and roles of circRNAs in macrophage polarization have not been well elucidated. Here, circRNAs expression profiles were determined in human THP-1 macrophages incubated in conditions causing activation toward M1 (interferon-γ + LPS) or M2 (interleukin-4) phenotypes. Overall, 9,720 circular RNA were detected from RNA sequencing data. Compared with M2 macrophages, a total of 140 circRNAs were aberrantly expressed in M1 macrophages, including 71 up-regulated circRNAs and 69 down-regulated circRNAs. Quantitative real-time PCR (qRT-PCR) results were generally consistent with the selected differentially expressed circRNAs. Gene Ontology (GO) and KEGG pathway analyses were used to predict biological functions and potential mechanisms of the host linear transcripts of these up-regulated and down-regulated circRNAs. Furthermore, we found that the expression level of circRNA-RNF19B (circRNF19B) in M1 macrophages was significantly higher than that in THP-1 macrophages and M2 macrophages. circRNF19B expression was increased when M2 converted to M1 whereas decreased when M1 converted to M2. Knockdown of circRNF19B following the activation of THP-1 cells using interferon-γ + LPS diminished the expression of M1 macrophages markers and elevated the expression of M2 macrophages markers. In conclusion, these data suggest the involvement of altered circRNAs expression patterns in macrophages exposure to different activating conditions. Circular RNAs may play important roles in regulating macrophage polarization.
巨噬细胞极化是巨噬细胞根据周围微环境发挥不同功能的过程。巨噬细胞通常存在于两种不同的亚群中：经典活化的M1巨噬细胞和替代活化的M2巨噬细胞。环状RNA（circRNAs）是一类通过反向剪接产生的新型非编码RNA。在不同的细胞和组织中鉴定出了数千种circRNAs。最近的研究表明，circRNAs在调节转录和转录后基因表达中起关键作用。然而，circRNAs在巨噬细胞极化中的作用和影响尚未得到充分阐明。在此，在诱导向M1（干扰素-γ+脂多糖）或M2（白细胞介素-4）表型活化的条件下培养的人THP-1巨噬细胞中测定了circRNAs表达谱。总体而言，从RNA测序数据中检测到9720种环状RNA。与M2巨噬细胞相比，M1巨噬细胞中共有140种circRNAs异常表达，包括71种上调的circRNAs和69种下调的circRNAs。定量实时PCR（qRT-PCR）结果与所选差异表达的circRNAs基本一致。基因本体（GO）和KEGG通路分析用于预测这些上调和下调circRNAs的宿主线性转录本的生物学功能和潜在机制。此外，我们发现circRNA-RNF19B（circRNF19B）在M1巨噬细胞中的表达水平显著高于THP-1巨噬细胞和M2巨噬细胞。当M2转化为M1时，circRNF19B表达增加，而当M1转化为M2时，circRNF19B表达降低。使用干扰素-γ+脂多糖激活THP-1细胞后敲低circRNF19B可降低M1巨噬细胞标志物的表达并提高M2巨噬细胞标志物的表达。总之，这些数据表明circRNAs表达模式的改变参与了巨噬细胞暴露于不同激活条件的过程。环状RNA可能在调节巨噬细胞极化中起重要作用。
