title: Involvement of retinoic acid signaling in goldfish optic nerve regeneration.
abstract: Recently, we identified a retina-specific retinol-binding protein, purpurin, as a trigger molecule in the early stage of goldfish optic nerve regeneration. Purpurin protein was secreted by photoreceptors to injured ganglion cells, at 2-5 days after optic nerve injury. Purpurin bound to retinol induced neurite outgrowth in retinal explant cultures and retinoic acid (RA) had a comparable effect on neurite outgrowth. These results indicate that purpurin acts as a retinol transporter and facilitates conversion of retinol to RA. Intracellularly, RA is transported into the nucleus with cellular retinoic acid-binding protein IIb (CRABPIIb) and binds with retinoic acid receptor alpha (RARalpha) as a transcriptional regulator of target genes. Here, we investigated the RA signaling through RA synthesis to RARalpha in the goldfish retina during optic nerve regeneration by RT-PCR. Retinaldehyde dehydrogenase 2 (RALDH2; an RA synthetic enzyme) mRNA was increased by 2.7-fold in the retina at 7-10 days and then gradually decreased until 40 days after nerve injury. In contrast, cytochrome P450 26a1 (CYP26a1; an RA degradative enzyme) mRNA was decreased to less than half in the retina at 5-20 days and then gradually returned to the control level by 40 days after nerve injury. CRABPIIb mRNA was increased by 1.5-fold in the retina at 10 days after axotomy, RARalphaa mRNA was increased by 1.8-fold in the retina at 10 days after axotomy. The cellular changes in the RA signaling molecules after optic nerve injury were almost all located in the ganglion cells, as evaluated by in situ hybridization. The present data described for the first time that RA signaling through RALDH2 and CRABPIIb to RARalpha was serially upregulated in the ganglion cells at 7-10 days just after the purpurin induction. Therefore, we conclude that the triggering action of purpurin on optic nerve regeneration is mediated by RA signaling pathway.
authors.affiliation: Kanazawa University, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Nagashima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mawatari
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Koriyama
authors.forename: Toru
authors.initials: T
authors.lastname: Matsukawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D006054:Goldfish; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000378:metabolism* / Q000503:physiopathology; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D050697:Retinal Dehydrogenase / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D000880:Anthraquinones; C502200:Crabp2a protein, zebrafish; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D029961:Zebrafish Proteins; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; C000607085:cyp26a1 protein, zebrafish; C518907:Aldh1a2 protein, zebrafish; D050697:Retinal Dehydrogenase; C511975:purpurin anthraquinone