April 11, 2014
Manuscript number: 1043690064103575
Title: Clinical significance of mTOR, ZEB1, ROCK1 expression in lung tissues of pulmonary
fibrosis patients
Dear Prof. Mark Dransfield and Edwin Roger Parra,
Thank you for your positive response to our article. We appreciate the feedback and have
strove to incorporate that feedback into our article. We used underlined letters for revised
sentences in the manuscript.
Reviewers’ comments
Major Compulsory Revisions
1. All the work is based in the observation of the expression of mTOR, ZEB1, and ROCK1 in
patients with IPF as if shows in the Abstract, introduction and discussion of the manuscript
but the author have IPF patients and connective tissue diseases (CTDs) with UIP pattern. The
authors can eliminate the 4 patients with CTDs or explain this other condition in the
introduction and in the discussion.
 We corrected abstract, introduction, discussion and conclusion section to clarify the
inclusion of CTD-related interstitial lung disease (CTD-ILD) on page 4, 7, 14 and 15.
2. If the authors don’t exclude these patients with CTDs, they need explain that these other
patients have a CTD with UIP histologic pattern, too
 All of the 4 CTD-ILD patients showed UIP features in lung tissue. We explained about this
in methods and Results section (page 7, 10).
3. If the authors don’t exclude the CTDs/UIP please explain in the results, that in this work
the authors didn't observe different characteristics when compared with IPF/UIP, Is it true?
 Baseline pulmonary function and each IHC scores were not different in patients with IPF
and CTD-ILD. We added Table 2 that compared clinical characteristics of IPF and CTD-
ILD.
4. Please comment still in the conclusion that in this work the authors didn’t observed
differences between IPF/UIP and CTDs/UIP (immunohistochemistry, pulmonary function
test or scores).
 Baseline pulmonary function and each IHC scores were not different in patients with IPF
and CTD-ILD. After excluding 4 patients with CTD-ILD, change of lung function decline
and fibrosis scores were related to the mTOR and ZEB1 expression level. We mentioned
about it in Table 2, Results, Discussion section (page 10, 14).
Minor Essential Revisions
1. Please change the H&E from figure 1 by panoramic view (10X) to show the differences
between the two principal grades of fibrosis.
 We changed figure 1 to low-power image as you recommend and corrected figure legend
(page 21).
2. In the Figure 1 please change all the panel of immunohistochemistry by others on 200X or
400X to show the grade of intensity and try to the put similar regions.
 We changed figure 1 as you recommend and corrected Figure legend (page 21).
3. Please change the figure 2 (D,E,F,G,H,I,J,K and L) with others on 200x or 400x to
observed much better the immunostaining of the cells. The figure 2 (H), I think, it isn’t a
fibroblastic foci. The authors need to be careful with the color of the figures.
 We corrected figure 2 and Results section as you recommend (Page 10, 21).
On behalf of all authors,
Young Whan Kim, M.D. Ph.D.
Professor
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and
Lung Institute of Medical Research Center, Seoul National University College of Medicine,
101 Daehangno, Jongno-gu, Seoul 110-744, Korea
E-mail: ywkim@snu.ac.kr Phone: +82-2-2072-2856, Fax: +82-2-762-9662