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

Mingyu Jiang; Jicheng Dai; Mingying Yin; Chunming Jiang; Mingyong Ren; Lin Tian

doi:10.1080/07853890.2021.1969033

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

Ann Med. 2021 Dec;53(1):1576-1588. doi: 10.1080/07853890.2021.1969033.

Authors

Mingyu Jiang¹, Jicheng Dai¹, Mingying Yin², Chunming Jiang¹, Mingyong Ren¹, Lin Tian³

Affiliations

¹ Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China.
² Department of Pediatrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, P. R. China.
³ Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China.

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 MessagesLncRNA 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.

Keywords: Henoch–Schonlein purpura; macrophage polarization; maternally expressed gene 8; miR-181a-5p; suppressor of SH2 domain-containing tyrosine phosphatase 2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Down-Regulation
Humans
IgA Vasculitis* / genetics
Janus Kinase 2 / genetics
Macrophages
MicroRNAs / genetics*
MicroRNAs / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics*
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction
STAT3 Transcription Factor / genetics

Substances

MicroRNAs
RNA, Long Noncoding
STAT3 Transcription Factor
Janus Kinase 2
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Ptpn11 protein, rat

Grants and funding

This study was financially supported by Heilongjiang Provincial Universities, projects of basic scientific research business funds, from the Education Department of Heilongjiang Province (2019-KYYWF-0332).