LncRNA MEG8 sponging miR-181a-5p contributes to M1 macrophage polarization by regulating SHP2 expression in Henoch-Schonlein purpura rats

Abstract

Background Long noncoding RNAs (LncRNAs) are regulatory molecules that play important roles in various biological and pathological processes. Herein, we aimed to explore whether maternally expressed gene 8 (MEG8) promotes M1 macrophage polarization among Henoch-Schonlein purpura (HSP) rats, and to investigate the underlying mechanism. Methods Relative mRNA expression of MEG8, miR-181a-5p and suppressor of SH2 domain-containing tyrosine phosphatase 2 (SHP2) were examined using quantitative reverse transcription polymerase chain reaction. Furthermore, expression of SHP2 and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway-related proteins was identified using western blot. Luciferase activity assay was conducted to evaluate whether miR-181a-5p could bind to MEG8 or SHP2. The macrophage phenotype was determined using flow cytometry and enzyme-linked immunosorbent assay. Results We observed macrophage polarization towards the M2 phenotype in the peripheral blood of HSP rats. Furthermore, MEG8 and SHP2 expression were down-regulated, while miR-181a-5p was up-regulated in monocyte-derived macrophages from the HSP rats compared to the control group. Furthermore, MEG8 functioned as a sponge for miR-181a-5p in order to facilitate SHP2 expression. Moreover, miR-181a-5p mimic and SHP2 knockdown significantly reversed the MEG8 overexpression-mediated suppression of JAK2/STAT3 signalling, and promotion of M1 polarization. Conclusions The lncRNA MEG8 sponged miR-181a-5p, which contributes to M1 macrophage polarization by regulating SHP2 expression in HSP rats. Key Messages LncRNA MEG8 downregulation and M2 polarization in Henoch Schonlein purpura rats. MEG8 upregulation enhances M1 polarization and suppresses JAK2/STAT3 pathway. MEG8 sponges miRNA-181a-5p to regulate SHP2 expression. MiRNA-181a-5p upregulation reverses lncRNA MEG8-mediated enhancement of M1 polarization and inhibition of JAK2/STAT3 pathway. SHP2 downregulation reverses lncRNA MEG8-mediated enhancement of M1 polarization and inhibition of JAK2/STAT3 pathway.

Long noncoding RNA MEG8 induces an imbalance of Th17/Treg cells through the miR-107/STAT3 axis in Henoch-Schonlein purpura rats

“…Nonetheless, MEG8 involvement within HSP is yet unclear. Previously, we found that MEG8 was expressed at low levels in RMDM-enhanced M1 macrophages polarization within HSP rats [15]. Further experiments in this research demonstrated that MEG8 reverses Th17/Treg imbalance within HSP CD4+ T-cell population, thereby providing novel insights into the MEG8 mechanism of action in HSP.…”

Adenovirus 14p1 induced changes in miRNA expression increases lung immunopathogenesis

“…However, others have reported that many of the miRNA associated with Ad14 infection can regulate inflammatory responses, ALI/ARDS and other lung inflammatory diseases. For example, increased expression of miR-181a-5p decreases NK-κB activation and alleviates inflammatory responses in COPD, whereas miR-181a-5p inhibition contributes to macrophage M1 polarization [88,89]. Increased expression of miR-27a-3p decreases expression of TNFα and IL6, while increased expression of let-7a-5p decreases expression of TNFα, IL6 and IL1β [73,90].…”

Renal Tissue miRNA Expression Profiles in ANCA-Associated Vasculitis—A Comparative Analysis

“…Characterized in a Henoch-Schönlein purpura rat model, SH2-domain-containing tyrosine phosphatase 2 (SHP2) is another potential modulator of macrophage polarization due to its inhibitory effect on the M2 polarization-promoting STAT3 signaling pathway while also actively inducing M1 polarization. Conversely, SHP2 has been considered to be a plausible target of hsa-miR-181a-5p, which could result in SHP2 under-expression and thus the disinhibition of STAT3 signaling [ 15 ]. Indeed, hsa-miR-181a-5p was among those differentially expressed in our AAV sample pool.…”