PONE-D-19-21143

Airway epithelial specific deletion of Jun-N-terminal kinase 1 attenuates pulmonary fibrosis in two independent mouse models

PLOS ONE

Dear Dr. van der Velden,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process, in particular, additional information regarding materials and methods and more discussion about the potential mechanisms underlying epithelial JNK1 knockout in attenuating lung fibrosis.  

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PLOS ONE

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Additional Editor Comments (if provided):

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In materials and methods, chemical and antibodies, the concentration of actin antibody should be checked. 1:500 or 1:5000?

In human lung tissues, the authors should write how many patient tissues are studied.

The authors should identificate whether the patients studied are male or female.

The authors should write ethic committee approval number for clinic and all animal studies.

In phospho-JNK staining human lung tissues, the authors should write incubation time and degree of antibody. The method should write more detaily.

In animals, the authors should write male or female mice?

The start of experiment, administered substance day and end of experiment should be schematized.

In gene expression, the authors should explain to use protocol that taqman or sybr green?

In results and in figure 1, the authors Said that JNK1 (JNK1/2) and JNK2 (JNK2/1). These are not clearly. They should explain.

In figures, "the collegen content score" should be expressed instead of the score (trichrome).

"fold induction of gene expression" should be expressed instead of fold induction.

Reviewer #2: In this manuscript, the authors addressed the role of epithelial JNK1 activation in the pathogenesis of lung fibrosis using both the bleomycin and AdTGFbeta1 models. The authors demonstrated nicely that activation of JNK1 occurred in both models of lung fibrosis in mice as well as in human IPF, epithelial deletion of JNK1 protected mice from fibrosis in both models, and finally delayed epithelial deletion of JNK1 resulted in reversal of existing fibrotic response. The experiments were well-controlled, the inducible epithelial JNK1 deletion model was sufficiently described and verified, and the analyses of fibrosis were adequate and convincing. I only have one question/concern:

The fact that epithelial deletion of JNK1 offered protection against lung fibrosis induced by both bleomycin and AdTGFbeta1 suggests that JNK1 works downstream of or in concert with TGFbeta1 in the fibrotic process. The fibrotic response in the bleomycin model, however, occurs subsequent to epithelial injury and inflammation. What is the role of JNK1 activation in lung injury and inflammation induced by bleomycin? If epithelial JNK1 deletion alters the injury/inflammatory response induced by bleomycin, then its effects on fibrosis would be secondary.

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Reviewer #1: No

Reviewer #2: No

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Airway epithelial specific deletion of Jun-N-terminal kinase 1 attenuates pulmonary fibrosis in two independent mouse models

PONE-D-19-21143R1

Dear Dr. van der Velden,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Wei Shi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No