The expression of MFGE8 in ischemic brain injury and its regulation of macrophage polarization
10.19845/j.cnki.zfysjjbzz.2021.0233
- VernacularTitle: MFGE8在缺血性脑损伤中表达及对巨噬细胞极化的调控作用
- Author:
Zheng LIU
1
;
Zhaohui WANG
1
;
Chunting ZHOU
1
Author Information
1. Department of Neurology,Hanyang Hospital,Wuhan University of Science and Technology（Wuhan Hanyang Hospital）,Wuhan 430050,China
- Publication Type:Journal Article
- Keywords:
Milk fat globule-epidermal growth factor 8;
Ischemic brain injury;
Macrophage polarization;
PI3K/Akt/mTOR signaling pathway
- From:
Journal of Apoplexy and Nervous Diseases
2021;38(10):1065-1069
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression of protein tyrosine kinase 2 (MFGE8) in patients with ischemic brain injury (IBI) and its regulation on macrophage polarization.Methods ELISA was used to detect the expression of MFGE8 protein in peripheral blood of patients with ischemic stroke and middle cerebral artery occlusion (MCAO) rat models;IF was used to detect the localization and expression of MFGE8 in brain;BV-2 microglia was treated with the culture supernatant of N2a neuronal cells (Mfge8CA) stably transformed with Mfge8.The polarization ratio of macrophages was detected by flow cytometry.Western blot detection Mfge8,αv/β 3-integrin,FAK,NF-κB.ERK1/2,JNK1/2,P38,PI3K,AKT,mTOR protein expression.Results The relative content of MFGE8 in peripheral blood of IBI patients and MCAO model rats was significantly lower than that of the control group (Ctrl,P=0.0446,P=0.0259).MFGE8 was highly co-localized with neuron cell marker (NeuN);the proportion of M1 type (CD45+F4/80+iNOS+Arginase1-) macrophages in the brain tissue of MCAO model was significantly higher than that in the Ctrl (P=0.0004).The proportion of M2 type (CD45+F4/80+iNOS-Arginase1+) macrophages was significantly lower than that of the Ctrl (P<0.0001).The proportion of M1 macrophages of BV-2 microglia after supernatant of N2a (mfge8CA) treatment was significantly lower than that of Wild type (WT,P=0.0230).The proportion of M2 macrophages was significantly higher (P<0.0001).The protein expressions of α v/β3-integrin,FAK,p-P85,P85,p-AKT (Ser473),p-mTOR (Ser2481) and p-mTOR (Ser2488) in BV-2 microglia after supernatant of N2a (mfge8CA) treatment were significantly higher than those in WT group.The expression of p-P65 protein was significantly lower than that in WT group.Conclusion MFGE8 is highly expressed in peripheral blood of patients with IBI.MFGE8 derived from neuronal cells may promote BV-2 microglia M2 macrophages polarization by activating PI3K/AKT/mTOR signals,and inhibit the polarization of M1 macrophages.
- Full text:20240729090211723281The expression of MFGE8 in ischemic brain injury and its regulation of macrophage polarization.pdf
