Pro-resolving mediator protectin D1 promotes epimorphic regeneration by controlling immune cell function in vertebrates.

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dc.coverageDOI: 10.1111/bph.15156
dc.creatorNguyen-Chi, Mai
dc.creatorLuz-Crawford, Patricia
dc.creatorBalas, Laurence
dc.creatorSipka, Tamara
dc.creatorContreras-López, Rafael
dc.creatorBarthelaix, Audrey
dc.creatorLutfalla, Georges
dc.creatorDurand, Thierry
dc.creatorJorgensen, Christian
dc.creatorDjouad, Farida
dc.date2020
dc.date.accessioned2025-11-18T19:47:10Z
dc.date.available2025-11-18T19:47:10Z
dc.description<p>Background and Purpose: Specialized pro-resolving mediators (SPMs) are a family of lipids controlling the resolution of inflammation and playing a role in many processes including organ protection and tissue repair. While SPMs are potent bioactive molecules in vivo, their role in epimorphic regeneration of organs in vertebrates has not been tested. Using the zebrafish larva as a robust regenerative vertebrate system, we studied the role of the SPM neuroprotectin/protectin D1 (PD1) during the caudal fin fold regeneration. Experimental Approach: Regeneration of the fin fold was analysed when exposed to a synthetic PD1. The effect of PD1 on immune cell recruitment and activation was further investigated using live imaging combined with fluorescent reporter lines. Using genetic and pharmacological approaches, we dissected the role of neutrophils and macrophages on driving the pro-regenerative effect of PD1. Key Results: We showed that PD1 improves fin fold regeneration. Acting in a narrow time window during regeneration, PD1 accelerates the resolution of inflammation without affecting the initial kinetic of neutrophil recruitment but instead, promotes their reverse migration potential. In addition, PD1 induces macrophage polarization switch towards non-inflammatory states in both zebrafish and mammalian system. Finally, macrophages but not neutrophils are essential for PD1-mediated regeneration. Conclusion and Implications: These results reveal the pro-regenerative action of PD1 and its role in regulating neutrophil and macrophage response in vertebrates. These findings strongly support the development of pro-resolving mediators as natural therapeutic candidates for degenerative disorders and the use of the zebrafish as a tool to investigate pro-regenerative drugs.</p>eng
dc.descriptionBackground and Purpose<br/>Specialized pro-resolving mediators (SPMs) are a family of lipids controlling the resolution of inflammation and playing a role in many processes including organ protection and tissue repair. While SPMs are potent bioactive molecules in vivo, their role in epimorphic regeneration of organs in vertebrates has not been tested. Using the zebrafish larva as a robust regenerative vertebrate system, we studied the role of the SPM neuroprotectin/protectin D1 (PD1) during the caudal fin fold regeneration.<br/><br/>Experimental Approach<br/>Regeneration of the fin fold was analysed when exposed to a synthetic PD1. The effect of PD1 on immune cell recruitment and activation was further investigated using live imaging combined with fluorescent reporter lines. Using genetic and pharmacological approaches, we dissected the role of neutrophils and macrophages on driving the pro-regenerative effect of PD1.<br/><br/>Key Results<br/>We showed that PD1 improves fin fold regeneration. Acting in a narrow time window during regeneration, PD1 accelerates the resolution of inflammation without affecting the initial kinetic of neutrophil recruitment but instead, promotes their reverse migration potential. In addition, PD1 induces macrophage polarization switch towards non-inflammatory states in both zebrafish and mammalian system. Finally, macrophages but not neutrophils are essential for PD1-mediated regeneration.<br/><br/>Conclusion and Implications<br/>These results reveal the pro-regenerative action of PD1 and its role in regulating neutrophil and macrophage response in vertebrates. These findings strongly support the development of pro-resolving mediators as natural therapeutic candidates for degenerative disorders and the use of the zebrafish as a tool to investigate pro-regenerative drugs.spa
dc.identifierhttps://investigadores.uandes.cl/en/publications/c6184440-3a8f-407a-b7e6-576049827faf
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/54900
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.177 (2020) date: 2020-09-01 nr.17 p.4055-4073
dc.subjectCD59 antigen
dc.subjectProtectin D1
dc.subjectTumor necrosis factor
dc.subjectunclassified drug
dc.titlePro-resolving mediator protectin D1 promotes epimorphic regeneration by controlling immune cell function in vertebrates.eng
dc.typeArticleeng
dc.typeArtículospa
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