PUBLICATION

Inhibition of TGF-β/Smad3 Signaling Disrupts Cardiomyocyte Cell Cycle Progression and Epithelial-Mesenchymal Transition-Like Response During Ventricle Regeneration

Authors
Peng, Y., Wang, W., Fang, Y., Hu, H., Chang, N., Pang, M., Hu, Y.F., Li, X., Long, H., Xiong, J.W., Zhang, R.
ID
ZDB-PUB-210407-65
Date
2021
Source
Frontiers in cell and developmental biology   9: 632372 (Journal)
Registered Authors
Zhang, Ruilin
Keywords
EMT-like response, Smad3, TGF-β, cell cycle, ventricle regeneration
Datasets
GEO:GSE162820
MeSH Terms
none
PubMed
33816481 Full text @ Front Cell Dev Biol
Abstract
Unlike mammals, zebrafish can regenerate injured hearts even in the adult stage. Cardiac regeneration requires the coordination of cardiomyocyte (CM) proliferation and migration. The TGF-β/Smad3 signaling pathway has been implicated in cardiac regeneration, but the molecular mechanisms by which this pathway regulates CM proliferation and migration have not been fully illustrated. Here, we investigated the function of TGF-β/Smad3 signaling in a zebrafish model of ventricular ablation. Multiple components of this pathway were upregulated/activated after injury. Utilizing a specific inhibitor of Smad3, we detected an increased ratio of unrecovered hearts. Transcriptomic analysis suggested that the TGF-β/Smad3 signaling pathway could affect CM proliferation and migration. Further analysis demonstrated that the CM cell cycle was disrupted and the epithelial-mesenchymal transition (EMT)-like response was impaired, which limited cardiac regeneration. Altogether, our study reveals an important function of TGF-β/Smad3 signaling in CM cell cycle progression and EMT process during zebrafish ventricle regeneration.
Errata / Notes
This article is corrected by ZDB-PUB-220906-244 .
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
fdu34Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDay 4
fdu34Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDay 5
fdu34Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDay 6
fdu34Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDays 7-13
fdu34Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazole, chemical treatment by environment: SIS3Day 4
fdu34Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazole, chemical treatment by environment: SIS3Day 5
fdu34Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazole, chemical treatment by environment: SIS3Day 6
fdu34Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazole, chemical treatment by environment: SIS3Days 7-13
fdu35Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazole, chemical treatment by environment: SIS3Days 7-13
fdu35Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazole, chemical treatment by environment: SIS3Days 7-13
1 - 10 of 45
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fdu34TgTransgenic Insertion
    fdu35TgTransgenic Insertion
      fdu36
        		Small Deletion
        pku371TgTransgenic Insertion
          s843TgTransgenic Insertion
            s957TgTransgenic Insertion
              sd10TgTransgenic Insertion
                1 - 7 of 7
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                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Target Reagent Reagent Type
                tgfb1bCRISPR6-tgfb1bCRISPR
                1 - 1 of 1
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                Fish
                Fish
                fdu34Tg; s957Tg
                fdu35Tg; s957Tg
                pku371Tg; s957Tg
                s843Tg; s957Tg
                s957Tg
                s957Tg; sd10Tg
                sd10Tg
                1 - 7 of 7
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                Antibodies
                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                EGFPEFGEGFP
                mAGFPEFGmAGFP
                mCherryEFGmCherry
                1 - 3 of 3
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                Mapping
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                Citation
                Peng, Y., Wang, W., Fang, Y., Hu, H., Chang, N., Pang, M., Hu, Y.F., Li, X., Long, H., Xiong, J.W., Zhang, R. (2021) Inhibition of TGF-β/Smad3 Signaling Disrupts Cardiomyocyte Cell Cycle Progression and Epithelial-Mesenchymal Transition-Like Response During Ventricle Regeneration. Frontiers in cell and developmental biology. 9:632372.