Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina.
Like other CNS neurons, mature retinal ganglion cells (RGCs) are unable to regenerate their axons after nerve injury due to a diminished intrinsic regenerative capacity. One of the reasons why they lose the capacity for axon regeneration seems to be associated with a dramatic shift in RGCs' pro...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3735487?pdf=render |
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| author | Yoshiki Koriyama Yusuke Takagi Kenzo Chiba Matsumi Yamazaki Kayo Sugitani Kunizo Arai Hirokazu Suzuki Satoru Kato |
| author_facet | Yoshiki Koriyama Yusuke Takagi Kenzo Chiba Matsumi Yamazaki Kayo Sugitani Kunizo Arai Hirokazu Suzuki Satoru Kato |
| author_sort | Yoshiki Koriyama |
| collection | DOAJ |
| description | Like other CNS neurons, mature retinal ganglion cells (RGCs) are unable to regenerate their axons after nerve injury due to a diminished intrinsic regenerative capacity. One of the reasons why they lose the capacity for axon regeneration seems to be associated with a dramatic shift in RGCs' program of gene expression by epigenetic modulation. We recently reported that (1R)-isoPropyloxygenipin (IPRG001), a genipin derivative, has both neuroprotective and neurite outgrowth activities in murine RGC-5 retinal precursor cells. These effects were both mediated by nitric oxide (NO)/S-nitrosylation signaling. Neuritogenic activity was mediated by S-nitrosylation of histone deacetylase-2 (HDAC2), which subsequently induced retinoic acid receptor β (RARβ) expression via chromatin remodeling in vitro. RARβ plays important roles of neural growth and differentiation in development. However, the role of RARβ expression during adult rat optic nerve regeneration is not clear. In the present study, we extended this hypothesis to examine optic nerve regeneration by IPRG001 in adult rat RGCs in vivo. We found a correlation between RARβ expression and neurite outgrowth with age in the developing rat retina. Moreover, we found that IPRG001 significantly induced RARβ expression in adult rat RGCs through the S-nitrosylation of HDAC2 processing mechanism. Concomitant with RARβ expression, adult rat RGCs displayed a regenerative capacity for optic axons in vivo by IPRG001 treatment. These neuritogenic effects of IPRG001 were specifically suppressed by siRNA for RARβ. Thus, the dual neuroprotective and neuritogenic actions of genipin via S-nitrosylation might offer a powerful therapeutic tool for the treatment of RGC degenerative disorders. |
| first_indexed | 2024-04-12T02:45:32Z |
| format | Article |
| id | doaj.art-afc1851517334eb7aed0eff8c38ad5e6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T02:45:32Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-afc1851517334eb7aed0eff8c38ad5e62022-12-22T03:51:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7125210.1371/journal.pone.0071252Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina.Yoshiki KoriyamaYusuke TakagiKenzo ChibaMatsumi YamazakiKayo SugitaniKunizo AraiHirokazu SuzukiSatoru KatoLike other CNS neurons, mature retinal ganglion cells (RGCs) are unable to regenerate their axons after nerve injury due to a diminished intrinsic regenerative capacity. One of the reasons why they lose the capacity for axon regeneration seems to be associated with a dramatic shift in RGCs' program of gene expression by epigenetic modulation. We recently reported that (1R)-isoPropyloxygenipin (IPRG001), a genipin derivative, has both neuroprotective and neurite outgrowth activities in murine RGC-5 retinal precursor cells. These effects were both mediated by nitric oxide (NO)/S-nitrosylation signaling. Neuritogenic activity was mediated by S-nitrosylation of histone deacetylase-2 (HDAC2), which subsequently induced retinoic acid receptor β (RARβ) expression via chromatin remodeling in vitro. RARβ plays important roles of neural growth and differentiation in development. However, the role of RARβ expression during adult rat optic nerve regeneration is not clear. In the present study, we extended this hypothesis to examine optic nerve regeneration by IPRG001 in adult rat RGCs in vivo. We found a correlation between RARβ expression and neurite outgrowth with age in the developing rat retina. Moreover, we found that IPRG001 significantly induced RARβ expression in adult rat RGCs through the S-nitrosylation of HDAC2 processing mechanism. Concomitant with RARβ expression, adult rat RGCs displayed a regenerative capacity for optic axons in vivo by IPRG001 treatment. These neuritogenic effects of IPRG001 were specifically suppressed by siRNA for RARβ. Thus, the dual neuroprotective and neuritogenic actions of genipin via S-nitrosylation might offer a powerful therapeutic tool for the treatment of RGC degenerative disorders.http://europepmc.org/articles/PMC3735487?pdf=render |
| spellingShingle | Yoshiki Koriyama Yusuke Takagi Kenzo Chiba Matsumi Yamazaki Kayo Sugitani Kunizo Arai Hirokazu Suzuki Satoru Kato Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina. PLoS ONE |
| title | Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina. |
| title_full | Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina. |
| title_fullStr | Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina. |
| title_full_unstemmed | Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina. |
| title_short | Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina. |
| title_sort | requirement of retinoic acid receptor β for genipin derivative induced optic nerve regeneration in adult rat retina |
| url | http://europepmc.org/articles/PMC3735487?pdf=render |
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