PMID- 34477472 OWN - NLM STAT- MEDLINE DCOM- 20211227 LR - 20231102 IS - 1365-2060 (Electronic) IS - 0785-3890 (Print) IS - 0785-3890 (Linking) VI - 53 IP - 1 DP - 2021 Dec TI - LncRNA MEG8 sponging miR-181a-5p contributes to M1 macrophage polarization by regulating SHP2 expression in Henoch-Schonlein purpura rats. PG - 1576-1588 LID - 10.1080/07853890.2021.1969033 [doi] AB - 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. FAU - Jiang, Mingyu AU - Jiang M AUID- ORCID: 0000-0002-0359-0064 AD - Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China. FAU - Dai, Jicheng AU - Dai J AD - Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China. FAU - Yin, Mingying AU - Yin M AD - Department of Pediatrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, P. R. China. FAU - Jiang, Chunming AU - Jiang C AD - Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China. FAU - Ren, Mingyong AU - Ren M AUID- ORCID: 0000-0002-8779-2797 AD - Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China. FAU - Tian, Lin AU - Tian L AD - Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Ann Med JT - Annals of medicine JID - 8906388 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (STAT3 Transcription Factor) RN - EC 2.7.10.2 (Janus Kinase 2) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) RN - EC 3.1.3.48 (Ptpn11 protein, rat) SB - IM MH - Animals MH - Down-Regulation MH - Humans MH - *IgA Vasculitis/genetics MH - Janus Kinase 2/genetics MH - Macrophages MH - MicroRNAs/*genetics/metabolism MH - Protein Tyrosine Phosphatase, Non-Receptor Type 11/*genetics MH - RNA, Long Noncoding/*genetics/metabolism MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - STAT3 Transcription Factor/genetics PMC - PMC8425717 OTO - NOTNLM OT - Henoch-Schonlein purpura OT - macrophage polarization OT - maternally expressed gene 8 OT - miR-181a-5p OT - suppressor of SH2 domain-containing tyrosine phosphatase 2 COIS- No potential conflict of interest was reported by the author(s). EDAT- 2021/09/04 06:00 MHDA- 2021/12/28 06:00 PMCR- 2021/09/03 CRDT- 2021/09/03 12:15 PHST- 2021/09/03 12:15 [entrez] PHST- 2021/09/04 06:00 [pubmed] PHST- 2021/12/28 06:00 [medline] PHST- 2021/09/03 00:00 [pmc-release] AID - 1969033 [pii] AID - 10.1080/07853890.2021.1969033 [doi] PST - ppublish SO - Ann Med. 2021 Dec;53(1):1576-1588. doi: 10.1080/07853890.2021.1969033.