Antifibrotic Soluble Thy-1 Correlates with Renal Dysfunction in Chronic Kidney Disease

Round 1

Reviewer 1 Report (Previous Reviewer 2)

No further comment.

Author Response

Thanks for the evaluation of our manuscript.

Attached you find the final version after all changes requested by the reviewers. Reviewers 2 suggested following changes:

1. In Figure 2B, the picture of the eNOS-/- group looks not good. I suggest the authors replace it. And In Figures 2B and 2E, the scale bars are unclear; please replace them.

We included information about bar length in the Figure Legend. In addition, we included thicker bars into the images.

We replaced Fig 2B by another image.

2. It is better to present the individual data as dot plots (scatter plots).

Thanks for the suggestion. We changed the diagrams in Figure 2 to dot plots

Best regards,

Anja Saalbach

Reviewer 2 Report (New Reviewer)

The authors investigated the association of sThy-1 with clinical parameters in patients with CKD receiving hemodialysis treatment compared to individuals with preserved renal function. Moreover, they found renal expression of Thy-1 is increased in kidney fibrosis.

Furthermore, they demonstrated that sThy-1 concentrations significantly increased with deteriorating renal function, independent of the presence of diabetes. These data showed that Thy-1 might function as a renal-protective factor against fibrosis.

Overall, it is an interesting and clear article.

1.    In Figure 2B, the picture of the eNOS-/- group looks not good. I suggest the authors replace it. And In Figures 2B and 2E, the scale bars are unclear; please replace them.

2.    It is better to present the individual data as dot plots (scatter plots).

Author Response

Thanks for the positive evaluation of our study.

1. In Figure 2B, the picture of the eNOS-/- group looks not good. I suggest the authors replace it. And In Figures 2B and 2E, the scale bars are unclear; please replace them.

We included information about bar length in the Figure Legend. In addition, we included thicker bars into the images.

We replaced Fig 2B by another image.

2. It is better to present the individual data as dot plots (scatter plots).

Thanks for the suggestion. We changed the diagrams in Figure 2 to dot plots.

Best regards,

Anja Saalbach

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Saalbach et al found soluble Thy-1 increased in patients with type 2 diabetes, and associated with the loss of renal function. Furthermore, they found sThy-1 increased in serum, urine, and diabetic mice. Although this work is potentially interesting, it is not fully supportive for the conclusion. Major concerns:

1.       Although serum Thy-1 was correlated with serum creatinine, it did not show a correlation with eGFR.

2.       Urinary Thy-1 only increased in CKD stage G5, suggesting it was not a sensitive marker.

3.       Thy-1 increased in db/db mice model, however, what is its function? How it affected renal fibrosis?

4.       Serum Thy-1 showed a correlation with serum IL-6, an inflammation marker. However, Thy-1 could not be induced under inflammatory condition, such as TNFα/IL1β stimulation. What is the reason?

5.       What is the cell origin for Thy-1 expression? The co-localizing should be performed.

6.       This work only showed a very preliminary data for Thy-1 detection in serum, urine, diabetic mouse kidneys. However, how Thy-1 affect renal cell function? What are the mechanisms? From this manuscript, the reviewers could not get novel information on the above issues.

Reviewer 2 Report

Anja et al. investigated the relationship between sThy-1 and renal function in CKD patients. They also validated the results in the animal model. The results are solidate and convincing. However, I have some concerns.

1.      In the animal model, the found that sThy-1 expression is increased in CKD mice. I believe the purpose of animal experiment is verify the sThy-1 is a predictor or risk factor of CKD. But in the clinical cohort, they analyzed the independent factor of sThy-1. That means sThy-1 is the end point parameter rather than a predictor of CKD. I am very confused.

2.      What is the mechanism of sThy-1 in the anti-fibrotic of kidneys? I cannot get any data from the animal study.