PMID- 37530929 OWN - NLM STAT- MEDLINE DCOM- 20231130 LR - 20231130 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 46 IP - 6 DP - 2023 Dec TI - Runx1 Deficiency Promotes M2 Macrophage Polarization Through Enhancing STAT6 Phosphorylation. PG - 2241-2253 LID - 10.1007/s10753-023-01874-7 [doi] AB - Our previous study had demonstrated that Runx1 promoted LPS-induced macrophage inflammatory response, however, the role of Runx1 in M2 macrophage polarization still remains largely unknown. This study was conducted to investigate the role of Runx1 in IL-4/IL-13-induced M2 macrophage polarization and its potential regulatory mechanism. We found that exposure of macrophages to IL-4/IL-13 induced a remarkable increasement in Runx1 expression level. Specifically, we established genetically modified mice lacking Runx1 in myeloid cells, including macrophages. RNA-Seq was performed to identify differentially expressed genes (DEGs) between Runx1 knockout and WT control bone marrow-derived macrophages (BMDMs). We identified 686 DEGs, including many genes which were highly expressed in M2 macrophage. In addition, bioinformatics analysis indicated that these DEGs were significantly enriched in extracellular matrix-related processes. Moreover, RT-qPCR analysis showed that there was an obvious upregulation in the relative expression levels of M2 marker genes, including Arg1, Ym1, Fizz1, CD71, Mmp9, and Tgm2, in Runx1 knockout macrophages, as compared to WT controls. Consistently, similar results were obtained in the protein and enzymatic activity levels of Arg1. Finally, we found that the STAT6 phosphorylation level was significantly enhanced in Runx1 knockout macrophages, and the STAT6 inhibitor AS1517499 partly reduced the upregulated effect of Runx1 deficiency on the M2 macrophage polarization. Taken together, Runx1 deficiency facilitates IL-4/IL-13-induced M2 macrophage polarization through enhancing STAT6 phosphorylation. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Zhou, Siyuan AU - Zhou S AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. FAU - Zhao, Ting AU - Zhao T AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. FAU - Chen, Xuqiong AU - Chen X AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. FAU - Zhang, Wuwen AU - Zhang W AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. FAU - Zou, Xiaoyi AU - Zou X AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. FAU - Yang, Yi AU - Yang Y AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. FAU - Wang, Qinshi AU - Wang Q AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. FAU - Zhang, Ping AU - Zhang P AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. FAU - Zhou, Tong AU - Zhou T AD - Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. zhoutong_cn@hotmail.com. FAU - Feng, Tongbao AU - Feng T AD - Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China. fengtongbao@hotmail.com. LA - eng GR - 82000678/National Natural Science Foundation of China/ GR - CZQM2021014/Young Talent Development Plan of Changzhou Health Commission/ GR - NMUB2019315/Foundation of Science and Technology Development of Nanjing Medical University/ GR - SYH-3201160-0065/Special Fund Project for Laboratory Medicine Research of Jiangsu Medical Association/ GR - 2022CZBJ077/Changzhou High-Level Medical Talents Training Project/ PT - Journal Article DEP - 20230802 PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Core Binding Factor Alpha 2 Subunit) RN - 0 (Interleukin-13) RN - 207137-56-2 (Interleukin-4) RN - 0 (Runx1 protein, mouse) RN - 0 (STAT6 Transcription Factor) RN - 0 (Stat6 protein, mouse) SB - IM MH - Animals MH - Mice MH - Core Binding Factor Alpha 2 Subunit/genetics/metabolism/pharmacology MH - *Interleukin-13/metabolism MH - *Interleukin-4/pharmacology/metabolism MH - Macrophage Activation MH - Macrophages/metabolism MH - Phosphorylation MH - STAT6 Transcription Factor/metabolism OTO - NOTNLM OT - M2 macrophage OT - Runx1 OT - STAT6 OT - bioinformatics analysis EDAT- 2023/08/02 13:09 MHDA- 2023/11/27 12:43 CRDT- 2023/08/02 11:09 PHST- 2023/05/09 00:00 [received] PHST- 2023/07/06 00:00 [accepted] PHST- 2023/07/03 00:00 [revised] PHST- 2023/11/27 12:43 [medline] PHST- 2023/08/02 13:09 [pubmed] PHST- 2023/08/02 11:09 [entrez] AID - 10.1007/s10753-023-01874-7 [pii] AID - 10.1007/s10753-023-01874-7 [doi] PST - ppublish SO - Inflammation. 2023 Dec;46(6):2241-2253. doi: 10.1007/s10753-023-01874-7. Epub 2023 Aug 2.