Reviewer's report 
 Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor Title: 
 2  7 October 2006 Version: Date: 
 Wendy Mars Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
The authors are to be commended for the addition of the data on HGF; however, unfortunately, although it 
IS from a publication, the method they chose to enrich for HGF has an essential flaw in it that makes their conclusions invalid. When using a detergent free protein isolation method in liver, if one discards the pellet, 
one discards the matrix/membrane fraction which is where much of the HGF resides. In fact, the discarded 
fraction is the most important one with regards to whether or not the liver is actively processing HGF which is what they were hoping to analyze. I can recommend two solutions. The better solution is to repeat the experiment but instead of discarding the pellet, solubilize it in SDS with appropriate inhibitors (including 
amiloride and other serine protease inhibitors is essential here since uPA and plasmin also reside in this 
fraction). Alternatively, you can alter the text to reflect the fact that you are only looking at cytosolic HGF. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
The additional information provided makes this a much improved manuscript; however, there are a few 
things that must be corrected/clarified before publication. 
1. On page 7 in the purification section for HGF, the word is "Eluate"--not "Elute". 2. In thge HGF figure (which I hope will be redone), you need to label what your control lane is, put the null sign on the uPAR, and add the sizes. 
3. On page 11, I believe that the authors meant to write uPA instead of uPAR in the middle of the page 
("fibrin clearance is impaired in "uPAR" mice"). ------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I have no competing interests. 
Reviewer's report 
 Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor Title: 
 2  7 October 2006 Version: Date: 
 Wendy Mars Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
The authors are to be commended for the addition of the data on HGF; however, unfortunately, although it 
IS from a publication, the method they chose to enrich for HGF has an essential flaw in it that makes their conclusions invalid. When using a detergent free protein isolation method in liver, if one discards the pellet, 
one discards the matrix/membrane fraction which is where much of the HGF resides. In fact, the discarded 
fraction is the most important one with regards to whether or not the liver is actively processing HGF which is what they were hoping to analyze. I can recommend two solutions. The better solution is to repeat the experiment but instead of discarding the pellet, solubilize it in SDS with appropriate inhibitors (including 
amiloride and other serine protease inhibitors is essential here since uPA and plasmin also reside in this 
fraction). Alternatively, you can alter the text to reflect the fact that you are only looking at cytosolic HGF. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
The additional information provided makes this a much improved manuscript; however, there are a few 
things that must be corrected/clarified before publication. 
1. On page 7 in the purification section for HGF, the word is "Eluate"--not "Elute". 2. In thge HGF figure (which I hope will be redone), you need to label what your control lane is, put the null sign on the uPAR, and add the sizes. 
3. On page 11, I believe that the authors meant to write uPA instead of uPAR in the middle of the page 
("fibrin clearance is impaired in "uPAR" mice"). ------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I have no competing interests. 
Please review this paper.
user
Reviewer's report 
 Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor Title: 
 2  7 October 2006 Version: Date: 
 Wendy Mars Reviewer: 
Reviewer's report: 
General 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
The authors are to be commended for the addition of the data on HGF; however, unfortunately, although it 
IS from a publication, the method they chose to enrich for HGF has an essential flaw in it that makes their conclusions invalid. When using a detergent free protein isolation method in liver, if one discards the pellet, 
one discards the matrix/membrane fraction which is where much of the HGF resides. In fact, the discarded 
fraction is the most important one with regards to whether or not the liver is actively processing HGF which is what they were hoping to analyze. I can recommend two solutions. The better solution is to repeat the experiment but instead of discarding the pellet, solubilize it in SDS with appropriate inhibitors (including 
amiloride and other serine protease inhibitors is essential here since uPA and plasmin also reside in this 
fraction). Alternatively, you can alter the text to reflect the fact that you are only looking at cytosolic HGF. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
The additional information provided makes this a much improved manuscript; however, there are a few 
things that must be corrected/clarified before publication. 
1. On page 7 in the purification section for HGF, the word is "Eluate"--not "Elute". 2. In thge HGF figure (which I hope will be redone), you need to label what your control lane is, put the null sign on the uPAR, and add the sizes. 
3. On page 11, I believe that the authors meant to write uPA instead of uPAR in the middle of the page 
("fibrin clearance is impaired in "uPAR" mice"). ------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I have no competing interests. 
assistant