The Notch signal mediates macrophage polarization by regulating miR-125a/miR-99b expression. Issue 1 (4th December 2019)

• Record Type: Journal Article
• Authors: Li, Qian; He, Xia; Yu, Qiao; Wu, Yuan; Du, Mingyu; Chen, Jing; Peng, Fanyu; Zhang, Wenjun; Chen, Jie; Wang, Yan; Chen, Hanbo; Wang, Hairong; He, Dan; Wang, Qiang
• Is Part Of: Artificial cells, nanomedicine, and biotechnology. Volume 47:Issue 1(2019)
• Page Start: 833
• Page End: 843
• Publication Date: 2019-12-04
• Subjects: Notch signal -- macrophage -- miR-125a -- miR-99b; Artificial cells -- Periodicals; Nanotechnology -- Periodicals; Blood substitutes -- Periodicals; Tissue engineering -- Periodicals; Molecules -- Periodicals; Biotechnology -- Periodicals; 615.39
• DOI: 10.1080/21691401.2019.1576711
• Languages: English
• ISSNs: 2169-1401

Abstract

Abstract: 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-α 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.