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Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome

Innervation sustains cornea integrity. Pigment epithelium‐derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer of Resolvin D6 (RvD6si). Here, we resolved the structure of this lipid isolated from mouse tears after injured...

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Autores principales: Pham, Thang L., Kakazu, Azucena H., He, Jiucheng, Nshimiyimana, Robert, Petasis, Nicos A., Jun, Bokkyoo, Bazan, Nicolas G., Bazan, Haydee E. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362171/
https://www.ncbi.nlm.nih.gov/pubmed/34245621
http://dx.doi.org/10.1096/fj.202100686R
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author Pham, Thang L.
Kakazu, Azucena H.
He, Jiucheng
Nshimiyimana, Robert
Petasis, Nicos A.
Jun, Bokkyoo
Bazan, Nicolas G.
Bazan, Haydee E. P.
author_facet Pham, Thang L.
Kakazu, Azucena H.
He, Jiucheng
Nshimiyimana, Robert
Petasis, Nicos A.
Jun, Bokkyoo
Bazan, Nicolas G.
Bazan, Haydee E. P.
author_sort Pham, Thang L.
collection PubMed
description Innervation sustains cornea integrity. Pigment epithelium‐derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer of Resolvin D6 (RvD6si). Here, we resolved the structure of this lipid isolated from mouse tears after injured corneas were treated with PEDF + DHA. RvD6si synthesis was inhibited by fluvoxamine, a cytochrome P450 inhibitor, but not by 15‐ or 5‐LOX inhibitors, suggesting that the 4‐ and 17‐hydroxy of DHA have an R R‐ or S R‐configuration. The two compounds were chemically synthesized. Using chiral phase HPLC, four peaks of RvD6si(1‐4) from tears were resolved. The R R‐RvD6 standard eluted as a single peak with RvD6(1) while pure S R‐RvD6 eluted with RvD6(3). The addition of these pure mediators prompted a trigeminal ganglion transcriptome response in injured corneas and showed that R R‐RvD6 was the more potent, increasing cornea sensitivity and nerve regeneration. R R‐RvD6 stimulates Rictor and hepatocyte growth factor (hgf) genes specifically as upstream regulators and a gene network involved in axon growth and suppression of neuropathic pain, indicating a novel function of this lipid mediator to maintain cornea integrity and homeostasis after injury.
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spelling pubmed-83621712021-08-17 Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome Pham, Thang L. Kakazu, Azucena H. He, Jiucheng Nshimiyimana, Robert Petasis, Nicos A. Jun, Bokkyoo Bazan, Nicolas G. Bazan, Haydee E. P. FASEB J Research Articles Innervation sustains cornea integrity. Pigment epithelium‐derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer of Resolvin D6 (RvD6si). Here, we resolved the structure of this lipid isolated from mouse tears after injured corneas were treated with PEDF + DHA. RvD6si synthesis was inhibited by fluvoxamine, a cytochrome P450 inhibitor, but not by 15‐ or 5‐LOX inhibitors, suggesting that the 4‐ and 17‐hydroxy of DHA have an R R‐ or S R‐configuration. The two compounds were chemically synthesized. Using chiral phase HPLC, four peaks of RvD6si(1‐4) from tears were resolved. The R R‐RvD6 standard eluted as a single peak with RvD6(1) while pure S R‐RvD6 eluted with RvD6(3). The addition of these pure mediators prompted a trigeminal ganglion transcriptome response in injured corneas and showed that R R‐RvD6 was the more potent, increasing cornea sensitivity and nerve regeneration. R R‐RvD6 stimulates Rictor and hepatocyte growth factor (hgf) genes specifically as upstream regulators and a gene network involved in axon growth and suppression of neuropathic pain, indicating a novel function of this lipid mediator to maintain cornea integrity and homeostasis after injury. John Wiley and Sons Inc. 2021-07-10 2021-08 /pmc/articles/PMC8362171/ /pubmed/34245621 http://dx.doi.org/10.1096/fj.202100686R Text en © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Pham, Thang L.
Kakazu, Azucena H.
He, Jiucheng
Nshimiyimana, Robert
Petasis, Nicos A.
Jun, Bokkyoo
Bazan, Nicolas G.
Bazan, Haydee E. P.
Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome
title Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome
title_full Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome
title_fullStr Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome
title_full_unstemmed Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome
title_short Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome
title_sort elucidating the structure and functions of resolvin d6 isomers on nerve regeneration with a distinctive trigeminal transcriptome
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362171/
https://www.ncbi.nlm.nih.gov/pubmed/34245621
http://dx.doi.org/10.1096/fj.202100686R
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