NG2 expression in microglial cells affects the expression of neurotrophic and proinflammatory factors by regulating FAK phosphorylation.
Neural/glial antigen 2 (NG2), a chondroitin sulfate proteoglycan, is significantly upregulated in a subset of glial cells in the facial motor nucleus (FMN) following CNS injury. NG2 is reported to promote the resulting inflammatory reaction, however, the mechanism by which NG2 mediates these effects is yet to be determined. In this study, we examined the changes in NG2 expressing microglial cells in the FMN in response to facial nerve axotomy (FNA) in mice. Our findings indicated that NG2 expression was progressively induced and upregulated specifically in the ipsilateral facial nucleus following FNA. To further investigate the effects of NG2 expression, in vivo studies in NG2-knockout mice and in vitro studies in rat microglial cells transfected with NG2 shRNAs were performed. Abolition of NG2 expression both in vitro and in vivo resulted in increased expression of neurotrophic factors (nerve growth factor and glial derived neurotrophic factor), decreased expression of inflammatory mediators (tumor necrosis factor-α and interleukin-1β) and decreased apoptosis in the ipsilateral facial nucleus in response to FNA. Furthermore, we demonstrated the role of FAK in these NG2-induced effects. Taken together, our findings suggest that NG2 expression mediates inflammatory reactions and neurodegeneration in microglial cells in response to CNS injury, potentially by regulating FAK phosphorylation.
Department of Plastic Surgery, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
Lie
L
Zhu
Department of Ophthalmology, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
Qing
Q
Su
Department of Plastic Surgery, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
Xiang
X
Jie
Department of Plastic Surgery, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
Antang
A
Liu
Department of Plastic Surgery, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
Hui
H
Wang
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Beiping
B
He
Department of Plastic Surgery, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China.
Hua
H
Jiang
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D020220:Facial Nerve Injuries / Q000473:pathology; D065828:Facial Nucleus / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D005786:Gene Expression Regulation; D018345:Mice, Knockout; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D051417:Focal Adhesion Kinase 1; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C496051:Ptk2 protein, mouse