Inhibition of Retinal Ganglion Cell Axonal Outgrowth Through the Amino-Nogo-A Signaling Pathway
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- 作者：Yan Huo (1)
Xiao-Lei Yin (2)
Shu-Xing Ji (1)
Huan Zou (1)
Min Lang (1)
Zheng Zheng (1)
Xiao-Feng Cai (1)
Wei Liu (1)
Chun-Lin Chen (1)
Yuan-Guo Zhou (3)
Rong-Di Yuan (4)
Jian Ye (1) - 关键词：Amino ; Nogo ; Axonal outgrowth ; Central nervous system ; Integrin ; Signaling pathway
- 刊名：Neurochemical Research
- 出版年：2013
- 出版时间：July 2013
- 年：2013
- 卷：38
- 期：7
- 页码：1365-1374
- 全文大小：692KB
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Xiao-Lei Yin (2)
Shu-Xing Ji (1)
Huan Zou (1)
Min Lang (1)
Zheng Zheng (1)
Xiao-Feng Cai (1)
Wei Liu (1)
Chun-Lin Chen (1)
Yuan-Guo Zhou (3)
Rong-Di Yuan (4)
Jian Ye (1)
1. Department of ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
2. Department of ophthalmology, 305 Hospital of PLA, Beijing, China
3. Department of Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
4. Department of ophthalmology, Xinqiao Hospital, Third Military Medical University, Chongqing, China - ISSN：1573-6903
文摘
Nogo-A is a myelin-derived inhibitor playing a pivotal role in the prevention of axonal regeneration. A functional domain of Nogo-A, Amino-Nogo, exerts an inhibitory effect on axonal regeneration, although the mechanism is unclear. The present study investigated the role of the Amino-Nogo–integrin signaling pathway in primary retinal ganglion cells (RGCs) with respect to axonal outgrowth, which is required for axonal regeneration. Immunohistochemistry showed that integrin αv, integrin α5 and FAK were widely expressed in the visual system. Thy-1 and GAP-43 immunofluorescence showed that axonal outgrowth of RGCs was promoted by Nogo-A siRNA and a peptide antagonist of the Nogo-66 functional domain of Nogo-A (Nep1-0), and inhibited by a recombinant rat Nogo-A-Fc chimeric protein (?0). Western blotting revealed increased integrin αv and p-FAK expression in Nogo-A siRNA group, decreased integrin αv expression in ?0 group and decreased p-FAK expression in Nep1-0 group. Integrin α5 expression was not changed in any group. RhoA G-LISA showed that RhoA activation was inhibited by Nogo-A siRNA and ?0, but increased by Nep1-0 treatment. These results suggest that Amino-Nogo inhibits RGC axonal outgrowth primarily through the integrin αv signaling pathway.