title: Inhibition of retinal ganglion cell axonal outgrowth through the Amino-Nogo-A signaling pathway.
abstract: 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 (Nep1-40), and inhibited by a recombinant rat Nogo-A-Fc chimeric protein (Δ20). Western blotting revealed increased integrin αv and p-FAK expression in Nogo-A siRNA group, decreased integrin αv expression in Δ20 group and decreased p-FAK expression in Nep1-40 group. Integrin α5 expression was not changed in any group. RhoA G-LISA showed that RhoA activation was inhibited by Nogo-A siRNA and Δ20, but increased by Nep1-40 treatment. These results suggest that Amino-Nogo inhibits RGC axonal outgrowth primarily through the integrin αv signaling pathway.
authors.affiliation: Department of ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huo
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Yin
authors.forename: Shu-Xing
authors.initials: SX
authors.lastname: Ji
authors.forename: Huan
authors.initials: H
authors.lastname: Zou
authors.forename: Min
authors.initials: M
authors.lastname: Lang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zheng
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: Yuan-Guo
authors.initials: YG
authors.lastname: Zhou
authors.forename: Rong-Di
authors.initials: RD
authors.lastname: Yuan
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
mesh_terms: D000818:Animals; D001369:Axons; D001483:Base Sequence; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D039482:Integrin alpha5 / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D000070798:Nogo Proteins; D009900:Optic Nerve / Q000201:enzymology; D010766:Phosphorylation; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D014793:Visual Cortex / Q000201:enzymology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D039482:Integrin alpha5; D009185:Myelin Proteins; D000070798:Nogo Proteins; D034741:RNA, Small Interfering; C000603197:Rtn4 protein, rat; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020742:rhoA GTP-Binding Protein