Biotechnology Letters

, Volume 39, Issue 7, pp 1069–1077 | Cite as

MAPK/ERK signalling is required for zebrafish cardiac regeneration

Original Research Paper

Abstract

Objectives

To better understand the molecular mechanisms of regeneration and explore the potential signalling pathways as therapeutic targets for heart attacks.

Results

After treatment with the MEK inhibitor AZD6244 upon cardiac injury, the core members in MAPK/ERK signalling—mek and erk—demonstrate elevated expression, and these proteins are deposited at the injury site in zebrafish. pERK is also induced in non-cardiomyocytes near the injury site. Furthermore, the induced expression of a dominant-negative form of MEK1 inhibits zebrafish cardiac regeneration, characterized by increased cardiac fibrosis (a hallmark of regenerative failure), reduced or delayed production of regenerative myocardium, and migration of FLI1+ endothelial cells, without direct inhibition of cardiomyocyte proliferation.

Conclusion

Appropriate activation of MAPK/ERK signalling is essential for zebrafish cardiac regeneration.

Keywords

Cardiac regeneration MAPK/ERK signalling MEK pERK Zebrafish 

Notes

Acknowledgements

We thank Guangju Yu in our laboratory for the preliminary in vitro work, and all the other labmates for their help during the research. We also thank the members in the Device Platform for State Key Institute of Genetic Engineering at Fudan University for access to the instruments and help with their use. The research was supported in part by grants from the National Basic Research Program of China (MOST945300 and MOST944500; TPZ) and the National Science Foundation of China (31172173; TPZ).

Supporting information

Supplementary Figure 1—The cardiomyocyte proliferation index of hsp70l:dn-MEK1 was unaffected after heat shock compared to the control group. (a) After daily heat shock from 3 dpa to 7 dpa, no significant difference was seen in cardiomyocyte proliferation between wild-type and transgenic fish ventricles (b–c), although pERK expression was slightly reduced in the transgenic group (d). Statistics are shown in (e). CM: cardiomyocytes; HS: heat shock.

Supplementary Table 1—The primers used for synthesis of probes in ISH.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

Supplementary material

10529_2017_2327_MOESM1_ESM.tif (8.6 mb)
Supplementary material 1 (TIFF 8828 kb)
10529_2017_2327_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 15 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.State Key Laboratory of Genetic Engineering, Department of GeneticsFudan University School of Life SciencesShanghaiChina
  2. 2.Department of MedicineVanderbilt University School of MedicineNashvilleUSA

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