miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages
The Notch pathway plays critical roles in the differentiation and polarized activation of macrophages; however, the downstream molecular mechanisms underlying Notch activity in macrophages remain elusive. Our previous study has identified a group of microRNAs that mediate Notch signaling to regulate...
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doaj-09eadbe79b8d4a8e95a8af0fa00560f22020-11-24T22:42:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01327294570miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of MacrophagesFei Huang0Fei Huang1Jun-Long Zhao2Liang Wang3Chun-Chen Gao4Shi-Qian Liang5Dong-Jie An6Jian Bai7Yan Chen8Hua Han9Hong-Yan Qin10State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaDepartment of Stomatology, PLA Navy General Hospital, Beijing, ChinaState Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaDepartment of Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, ChinaThe Notch pathway plays critical roles in the differentiation and polarized activation of macrophages; however, the downstream molecular mechanisms underlying Notch activity in macrophages remain elusive. Our previous study has identified a group of microRNAs that mediate Notch signaling to regulate macrophage activation and tumor-associated macrophages (TAMs). In this study, we demonstrated that miR-148a-3p functions as a novel downstream molecule of Notch signaling to promote the differentiation of monocytes into macrophages in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF). Meanwhile, miR-148a-3p promoted M1 and inhibited M2 polarization of macrophages upon Notch activation. Macrophages overexpressing miR-148a-3p exhibited enhanced ability to engulf and kill bacteria, which was mediated by excessive production of reactive oxygen species (ROS). Further studies using reporter assay and Western blotting identified Pten as a direct target gene of miR-148a-3p in macrophages. Macrophages overexpressing miR-148a-3p increased their ROS production through the PTEN/AKT pathway, likely to defend against bacterial invasion. Moreover, miR-148a-3p also enhanced M1 macrophage polarization and pro-inflammatory responses through PTEN/AKT-mediated upregulation of NF-κB signaling. In summary, our data establish a novel molecular mechanism by which Notch signaling promotes monocyte differentiation and M1 macrophage activation through miR-148a-3p, and suggest that miR-148a-3p-modified monocytes or macrophages are potential new tools for the treatment of inflammation-related diseases.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01327/fullmacrophagesNotch signalingmiR-148a-3pPTENNF-κB |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fei Huang Fei Huang Jun-Long Zhao Liang Wang Chun-Chen Gao Shi-Qian Liang Dong-Jie An Jian Bai Yan Chen Hua Han Hong-Yan Qin |
spellingShingle |
Fei Huang Fei Huang Jun-Long Zhao Liang Wang Chun-Chen Gao Shi-Qian Liang Dong-Jie An Jian Bai Yan Chen Hua Han Hong-Yan Qin miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages Frontiers in Immunology macrophages Notch signaling miR-148a-3p PTEN NF-κB |
author_facet |
Fei Huang Fei Huang Jun-Long Zhao Liang Wang Chun-Chen Gao Shi-Qian Liang Dong-Jie An Jian Bai Yan Chen Hua Han Hong-Yan Qin |
author_sort |
Fei Huang |
title |
miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages |
title_short |
miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages |
title_full |
miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages |
title_fullStr |
miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages |
title_full_unstemmed |
miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages |
title_sort |
mir-148a-3p mediates notch signaling to promote the differentiation and m1 activation of macrophages |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-10-01 |
description |
The Notch pathway plays critical roles in the differentiation and polarized activation of macrophages; however, the downstream molecular mechanisms underlying Notch activity in macrophages remain elusive. Our previous study has identified a group of microRNAs that mediate Notch signaling to regulate macrophage activation and tumor-associated macrophages (TAMs). In this study, we demonstrated that miR-148a-3p functions as a novel downstream molecule of Notch signaling to promote the differentiation of monocytes into macrophages in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF). Meanwhile, miR-148a-3p promoted M1 and inhibited M2 polarization of macrophages upon Notch activation. Macrophages overexpressing miR-148a-3p exhibited enhanced ability to engulf and kill bacteria, which was mediated by excessive production of reactive oxygen species (ROS). Further studies using reporter assay and Western blotting identified Pten as a direct target gene of miR-148a-3p in macrophages. Macrophages overexpressing miR-148a-3p increased their ROS production through the PTEN/AKT pathway, likely to defend against bacterial invasion. Moreover, miR-148a-3p also enhanced M1 macrophage polarization and pro-inflammatory responses through PTEN/AKT-mediated upregulation of NF-κB signaling. In summary, our data establish a novel molecular mechanism by which Notch signaling promotes monocyte differentiation and M1 macrophage activation through miR-148a-3p, and suggest that miR-148a-3p-modified monocytes or macrophages are potential new tools for the treatment of inflammation-related diseases. |
topic |
macrophages Notch signaling miR-148a-3p PTEN NF-κB |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01327/full |
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