DUSP2 Deletion Inhibits Macrophage Migration by Inhibiting ERK Activation in Zebrafish

Round 1

Reviewer 1 Report

The authors presented that DUSP2 plays an important role in macrophage migration via Erk activation in zebrafish. The authors provided the investigation using zebrafish lines. Macrophage migration was imaged using fluorescence microscope. The author showed that zebrafish with tail fin injury expressed higher mRNA level of pro-inflammatory cytokines IL-1b, IL-8 and, TNFa and macrophage chemokines, CCL2 and CXCL11 compared to WT. However, the mRNA levels of TNFa and CXCL11 were not significantly different between WT and the DUSP2 mutant group. In addition, the authors represented that DUSP2 deletion attenuated Erk protein phosphorylation using PD325901.

The experimental designs were well organized. However, few details are warranted.

1.The authors should have mentioned the “n” number of zebrafish in each experiment.

2.The authors should mention how the to obtain the total number of macrophages.

3. The authors should provide the concentration of DMSO was currently in use.

4. The table 1, the text should be rearranged.

5. The authors did not give a reason why the CCL2 and CXCL11 was investigated rather than others. Figure 3, the result revealed mRNA levels of TNFa and CXCL11 were not significantly different between WT and the DUSP2 mutant group. Why not? this may help readers to understand.

6. Actually, neutrophils also play a crucial role in inflammation. However, the authors presented that neutrophils level did not show a significant difference in DUSP2 KO and control group. Why only macrophages?

7. Figure 6, western blot results of b-actin band of figure B should be equally presented each lane.

8. Figure 4A, 5A, 7B, and 8A, the image can be improved. It is difficult to determine.

Author Response

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Reviewer 2 Report

The manuscript "DUSP2 deletion inhibits macrophages migration by inhibiting ERK activation in zebrafish" by Yu-Jiao Li et al. is very interesting and adequately presented. However, I suggest enriching the discussions.

In the discussion section, the authors have limited themselves to commenting and summarizing their results. I would like the discussion section to be expanded with further bibliographical data and terms of comparison if any exist. I would also like to understand better if these experimental data can be applied in translational medicine.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

Dear Editor,

The manuscript entitled “DUSP2 deletion inhibits macrophages migration by inhibiting ERK activation in zebrafish” by Yu-Jiao Li et al. describes the study of DUSP2 effects on macrophages migration using the tail fin injury model in zebrafish larvae. The authors found that deletion of DUSP2 inhibited expression of pro-inflammatory cytokines and macrophage chemokines while live imaging results showed that migration of macrophages to the injury site was inhibited after DUSP2 deletion. Moreover, the authors found that the DUSP2 inhibitory effect was mediated through reduced activation of extracellular regulated protein kinases (ERK) in DUSP2 knockout zebrafish.

Τhe manuscripts’ objects are interesting, it well written in a comprehensive way and the findings are interesting. Therefore, the manuscript could be accepted for publication after minor revisions:

1. The authors should explain all abbreviation (e.g. dph, hpi, etc) when first appeared.

2. Where the used primers designed specifically for that study? If not please provide references for the primers.

3. Figures 4A, 5A, 7B and 8A are not schematic diagrams, they are images. Please correct. Similarly, figures 6A and 6B are not graphs but images.

4. The discussion section seems incomplete. Please add some more information and critical discussion on the proposed DUSP2 function and effects on macrophages migration.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf