PUBLICATION

Ciliary neurotrophic factor stimulates cardioprotection and the proliferative activity in the adult zebrafish heart

Authors
Bise, T., de Preux Charles, A.S., Ja?wi?ska, A.
ID
ZDB-PUB-190201-5
Date
2019
Source
NPJ Regenerative medicine   4: 2 (Journal)
Registered Authors
Jazwinska, Anna
Keywords
none
MeSH Terms
none
PubMed
30701084 Full text @ NPJ Regen Med
Abstract
Unlike mammals, adult zebrafish can regenerate their hearts after injury via proliferation of cardiomyocytes. The cell-cycle entry of zebrafish cardiac cells can also be stimulated through preconditioning by thoracotomy, a chest incision without myocardial damage. To identify effector genes of heart preconditioning, we performed transcriptome analysis of ventricles from thoracotomized zebrafish. This intervention led to enrichment of cardioprotective factors, epithelial-to-mesenchymal transition genes, matrix proteins and components of LIFR/gp130 signaling. We identified that inhibition of the downstream signal transducer of the LIFR/gp130 pathway through treatment with Ruxolitinib, a specific JAK1/2 antagonist, suppressed the cellular effects of preconditioning. Activation of LIFR/gp130 signaling by a single injection of the ligand Cilliary Neurotrophic Factor, CNTF, was sufficient to trigger cardiomyocyte proliferation in the intact heart. In addition, CNTF induced other pro-regenerative processes, including expression of cardioprotective genes, activation of the epicardium, enhanced intramyocardial Collagen XII deposition and leucocyte recruitment. These effects were abrogated by the concomitant inhibition of the JAK/STAT activity. Mutation of the cntf gene suppressed the proliferative response of cardiomyocytes after thoracotomy. In the regenerating zebrafish heart, CNTF injection prior to ventricular cryoinjury improved the initiation of regeneration via reduced cell apoptosis and boosted cardiomyocyte proliferation. Our findings reveal the molecular effectors of preconditioning and demonstrate that exogenous CNTF exerts beneficial regenerative effects by rendering the heart more resilient to injury and efficient in activation of the proliferative programs.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
ABlaceration: pericardial region, chemical treatment by environment: PD173074Adult
ABlaceration: pericardial region, chemical treatment by environment: PD173074Adult
ABlaceration: pericardial region, chemical treatment by environment: ruxolitinibAdult
ABlaceration: pericardial region, chemical treatment by environment: ruxolitinibAdult
ABlaceration: pericardial region, chemical treatment by environment: SB 431542Adult
ABlaceration: pericardial region, chemical treatment by environment: SB 431542Adult
ABlaceration: pericardial regionAdult
ABlaceration: pericardial regionAdult
ABlaceration: pericardial regionAdult
ABlaceration: pericardial regionAdult
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    fri3
      Small Deletion
      fri4
        Small Deletion
        gl22TgTransgenic Insertion
          sqet27EtTransgenic Insertion
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Fish
            1 - 4 of 4
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            Antibodies
            Orthology
            Engineered Foreign Genes
            Marker Marker Type Name
            DsRed2EFGDsRed2
            EGFPEFGEGFP
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            Mapping