PMID- 30862190 OWN - NLM STAT- MEDLINE DCOM- 20190729 LR - 20190729 IS - 2169-141X (Electronic) IS - 2169-1401 (Linking) VI - 47 IP - 1 DP - 2019 Dec TI - The Notch signal mediates macrophage polarization by regulating miR-125a/miR-99b expression. PG - 833-843 LID - 10.1080/21691401.2019.1576711 [doi] AB - We aimed to explore the mediating role of Notch signal in macrophage polarization. This signal was knocked out from macrophages of Lyz2 cre and RBP-J flox mice. Bone marrow-derived macrophages (BMDMs) were isolated and polarized. The expressions of polarization markers in BMDMs 24 h after transfection were detected by qPCR. After Notch knockout, the expressions of M1 markers decreased but those of M2 markers increased significantly. MiR-125a/miR-99b and Spaca6 were highly and lowly expressed upon M1 and M2 polarizations, respectively. The expressions of experimental group were significantly lower than those of control group. Overexpression of miR-125a significantly promoted the expressions of M1 markers, whereas inhibited those of M2 markers. NO release in the culture supernatant of miR-125a overexpression group significantly exceeded that of control group. Transfection with miR-125a inhibitor significantly down-regulated IL-12 expression but up-regulated MR expression in BMDMs. The supernatant secreted by M1 macrophages significantly facilitated BS524 cell apoptosis, which was enhanced after miR-125a overexpression. The TNF-alpha expression of miR-99b overexpression group increased whereas that of MR decreased significantly. The miR-125a/miR-99b cluster contained an RBP-J specific recognition site in the first intron of initial transcript. The Notch signalling pathway promoted macrophage polarization into M1 phenotype by up-regulating miR-125a/miR-99b expression. FAU - Li, Qian AU - Li Q AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - He, Xia AU - He X AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Yu, Qiao AU - Yu Q AD - b Department of General Surgery , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Wu, Yuan AU - Wu Y AD - c Department of Internal Medicine , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Du, Mingyu AU - Du M AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Chen, Jing AU - Chen J AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Peng, Fanyu AU - Peng F AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Zhang, Wenjun AU - Zhang W AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Chen, Jie AU - Chen J AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Wang, Yan AU - Wang Y AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Chen, Hanbo AU - Chen H AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Wang, Hairong AU - Wang H AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - He, Dan AU - He D AD - a Department of Radiation Oncology , Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University , Nanjing , PR China. FAU - Wang, Qiang AU - Wang Q AD - d Department of Radiation Oncology , Xuzhou Cancer Hospital , Xuzhou , PR China. LA - eng PT - Journal Article PT - Retracted Publication PL - England TA - Artif Cells Nanomed Biotechnol JT - Artificial cells, nanomedicine, and biotechnology JID - 101594777 RN - 0 (Biomarkers) RN - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein) RN - 0 (MicroRNAs) RN - 0 (Mirn125 microRNA, mouse) RN - 0 (Mirn99 microRNA, mouse) RN - 0 (Rbpj protein, mouse) RN - 0 (Receptors, Notch) RN - 0 (Seminal Plasma Proteins) RN - 0 (Spaca6 protein, mouse) RIN - Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):4273. PMID: 31738581 MH - Animals MH - Biomarkers/metabolism MH - Cell Line, Tumor MH - *Gene Expression Regulation MH - Gene Knockout Techniques MH - Humans MH - Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics MH - Macrophage Activation/genetics MH - Macrophages/cytology/*immunology/metabolism MH - Mice MH - Mice, Knockout MH - MicroRNAs/antagonists & inhibitors/*genetics MH - Phenotype MH - Receptors, Notch/genetics/*metabolism MH - Seminal Plasma Proteins/genetics MH - *Signal Transduction OTO - NOTNLM OT - Notch signal OT - macrophage OT - miR-125a OT - miR-99b EDAT- 2019/03/14 06:00 MHDA- 2019/07/30 06:00 CRDT- 2019/03/14 06:00 PHST- 2019/03/14 06:00 [entrez] PHST- 2019/03/14 06:00 [pubmed] PHST- 2019/07/30 06:00 [medline] AID - 10.1080/21691401.2019.1576711 [doi] PST - ppublish SO - Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):833-843. doi: 10.1080/21691401.2019.1576711.