Soluble NgR fusion protein modulates the proliferation of neural progenitor cells via the Notch pathway |
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Authors: | Li Xin Su Huanxing Fu Qing-Ling Guo Jiasong Lee Daniel H S So Kwok-Fai Wu Wutian |
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Institution: | (1) Department of Emergency, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan II, Guangzhou, 510080, Guangdong, China;(2) Department of Anatomy and The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China;(3) Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, Guangdong, China;(4) Roche R&D Center (China) Ltd, 720 Cai Lun Road, Building, Pudong, 201203, Shanghai, China;(5) Joint Laboratory for Brain Function and Health (BFAH), Jinan University and The University of Hong Kong, Guangzhou, China; |
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Abstract: | NogoA, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein are CNS myelin molecules that bind to
the neuronal Nogo-66 receptor (NgR) and inhibit axon growth. The NgR antagonist, soluble NgR1-Fc protein (sNgR-Fc), facilitates
axon regeneration by neutralizing the inhibitory effects of myelin proteins in experimental models of CNS injury. Here we
aim to investigate the effect of sNgR-Fc on the proliferation of neural progenitor cells (NPCs). The hippocampus cells of
embryonic rats were isolated and cultured in vitro. The expression of nestin, βIII-Tubulin, GFAP and Nogo-A on these cells
was observed using immunocytochemistry. In order to investigate the effect on proliferation of NPCs, sNgR-Fc, MAG-Fc chimera
and Notch1 blocker were added respectively. The total cell number for the proliferated NPCs was counted. BrdU was applied
and the rate of proliferating cells was examined. The level of Notch1 was analyzed using Western blotting. We identified that
NogoA is expressed in NPCs. sNgR-Fc significantly enhanced the proliferation of NPCs in vitro as indicated by BrdU labeling
and total cell count. This proliferation effect was abolished by the administration of MAG suggesting specificity. In addition,
we demonstrate that sNgR-Fc is a potent activator for Notch1 and Notch1 antagonist reversed the effect of sNgR-Fc on NPC proliferation.
Our results suggest that sNgR-Fc may modulate Nogo activity to induce NPC proliferation via the Notch pathway. |
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