PMID- 37087583 OWN - NLM STAT- MEDLINE DCOM- 20230504 LR - 20230504 IS - 1673-4254 (Print) IS - 2663-0842 (Electronic) IS - 1673-4254 (Linking) VI - 43 IP - 3 DP - 2023 Mar 20 TI - [M2 macrophage-derived exosomal lncRNA NR_028113.1 promotes macrophage polarization possibly by activating the JAK2/STAT3 signaling pathway]. PG - 393-399 LID - 10.12122/j.issn.1673-4254.2023.03.08 [doi] AB - OBJECTIVE: To explore the effect of M2 macrophage-derived exosomal lncRNA NR_028113.1 on macrophage polarization and its possible mechanism. METHODS: Bone marrow-derived macrophages (BMDMs) from BALB/c mice were isolated and cultured in vitro. After IL-4 treatment to induce M2 macrophage polarization, exosomes (M2-exo) were extracted from the supernatant of M2 macrophages and identified. The expression of lncRNA in M2-exo was detected by qRT-PCR. BMDMs were co-cultured with M2-exo (100 mug/mL) or PBS for 48 h, and the changes in cellular expression levels of Arg1, YM-1, FIZZ1, iNOS and TNF-alpha were detected using qRT-PCR and Western blotting. The percentage of CD206(+) cells was analyzed using flow cytometry, and the phosphorylation levels of JAK2/STAT3 proteins were detected using Western blotting. A lncRNA smart silencer was designed to specifically inhibit the expression of lncRNA NR_028113.1 in the M2 macrophages, from which exosomes were extracted and co-cultured with BMDMs for 48 h. The mRNA expression levels of Arg1, YM-1, FIZZ1, iNOS and TNF-alpha, CD206(+) cell percentage and the phosphorylation levels of JAK2/STAT3 proteins were detected using qRT-PCR, flow cytometry and Western blotting. RESULTS: LncRNA NR_028113.1 was highly expressed in the exosomes of M2 macrophages (P < 0.05). Co-culture with M2-exo significantly increased mRNA expressions of M2 macrophage marker genes Arg1, YM-1 and FIZZ1 (P < 0.05), lowered the expressions of iNOS and TNF-alpha (P < 0.05), and increased CD206(+) cell percentage and JAK2/STAT3 protein phosphorylation level in BMDMs (P < 0.05). After inhibiting the expression of lncRNA NR_028113.1 in M2 macrophages, the extracted M2-exo caused significant down-regulation of the mRNA expressions of Arg1, YM-1 and FIZZ1 and up-regulation of iNOS and TNF-alpha mRNA (P < 0.05), resulting also in signi-ficantly reduced CD206(+) cell percentage and lowered phosphorylation levels of JAK2/STAT3 proteins in co-cultured BMDM (P < 0.05). CONCLUSIONS: M2 macrophage-derived exosomal lncRNA NR_028113.1 can significantly promote M2 polarization of macrophages possibly by activating the JAK2/STAT3 signaling pathway. FAU - Zhang, M AU - Zhang M AD - Key Laboratory of Non- coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu 241001, China. AD - Central Laboratory, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China. FAU - Li, Z AU - Li Z AD - Department of Rheumatology, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China. FAU - Pei, W AU - Pei W AD - Key Laboratory of Non- coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu 241001, China. AD - Central Laboratory, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China. FAU - Li, X AU - Li X AD - Key Laboratory of Non- coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu 241001, China. AD - Central Laboratory, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China. FAU - Yang, H AU - Yang H AD - Key Laboratory of Non- coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu 241001, China. AD - Central Laboratory, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China. FAU - Zhu, X AU - Zhu X AD - Key Laboratory of Non- coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu 241001, China. AD - Central Laboratory, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China. FAU - Lu, K AU - Lu K AD - Key Laboratory of Non- coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu 241001, China. AD - Central Laboratory, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Nan Fang Yi Ke Da Xue Xue Bao JT - Nan fang yi ke da xue xue bao = Journal of Southern Medical University JID - 101266132 RN - EC 2.7.10.2 (Jak2 protein, mouse) RN - EC 2.7.10.2 (Janus Kinase 2) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Messenger) RN - 0 (STAT3 Transcription Factor) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Mice MH - Exosomes/genetics MH - Janus Kinase 2/metabolism MH - *Macrophage Activation/genetics MH - *Macrophages/metabolism MH - *RNA, Long Noncoding/genetics/metabolism MH - RNA, Messenger/metabolism MH - Signal Transduction/genetics MH - STAT3 Transcription Factor/metabolism MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC10122731 OTO - NOTNLM OT - JAK2 OT - STAT3 OT - exosomes OT - long non-coding RNA OT - macrophage polarization EDAT- 2023/04/23 06:41 MHDA- 2023/04/25 10:20 PMCR- 2023/03/20 CRDT- 2023/04/23 01:52 PHST- 2023/04/25 10:20 [medline] PHST- 2023/04/23 06:41 [pubmed] PHST- 2023/04/23 01:52 [entrez] PHST- 2023/03/20 00:00 [pmc-release] AID - nfykdxxb-43-3-393 [pii] AID - 10.12122/j.issn.1673-4254.2023.03.08 [doi] PST - ppublish SO - Nan Fang Yi Ke Da Xue Xue Bao. 2023 Mar 20;43(3):393-399. doi: 10.12122/j.issn.1673-4254.2023.03.08.