Title: miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to
inhibit the activation of hepatic stellate cells
Version: 3 Date: 31 Dec 2023
Reviewer's report:
Comment to author
reply for A1
>When is epigenetic downregulation likely to occur? This is the period when liver damage
occurs due to viruses or alcohol (acute phase), or when liver fibrosis occurs and liver
sinusoidal cells become capillary and become hypoxic, or even when extracellular matrix causes
pathological histopathology. Has liver fibrosis been confirmed?
Please give your opinion on this. This is related to the answer to Q5 that I commented on last
time.
Is it possible that we are seeing epigenetic silencing of miR-541 as a negative feedback after
liver fibrosis?
reply for A2
>Question 1 points out that suppression of miR-541 expression is related to epigenetic silencing.
If so, it is possible that similar results could be obtained with the cells that make up the liver, such
as hepatocytes, cylinder-like endothelial cells, and hepatic stellate cells. Similar suppression of
expression may also be observed in tissues other than liver tissues. I understand that you can't
analyze it because you don't have the materials, but please provide your opinion by including
the existing information.
reply for A5
>Related to Q1's comment earlier, please indicate at what point in fibrosis the Notch signal is
activated and whether this reaction is reversible.
LX2 cells become activated when TGF# is applied, and once activated, TGF# is removed and
the LX2 cells become quiescent again.
Why not consider how this phenomenon that the author points out changes using such an
experimental system?
reply for A7
>The importance of treatment for liver fibrosis differs depending on the state of mild liver
fibrosis and the state of liver cirrhosis. Furthermore, if liver fibrosis is mild, treatment response
can be expected, but otherwise it is expected to be difficult to obtain promising results. From
this point of view as well, in order to demonstrate the usefulness of gene therapy using miR-541,
it is extremely important to show that the miR-541/JAG2 axis that I discovered indicates which
phase of liver fibrosis is occurring.
There are no additional comments for comments A3, A4, and A6.
Title: miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to
inhibit the activation of hepatic stellate cells
Version: 3 Date: 31 Dec 2023
Reviewer's report:
Comment to author
reply for A1
>When is epigenetic downregulation likely to occur? This is the period when liver damage
occurs due to viruses or alcohol (acute phase), or when liver fibrosis occurs and liver
sinusoidal cells become capillary and become hypoxic, or even when extracellular matrix causes
pathological histopathology. Has liver fibrosis been confirmed?
Please give your opinion on this. This is related to the answer to Q5 that I commented on last
time.
Is it possible that we are seeing epigenetic silencing of miR-541 as a negative feedback after
liver fibrosis?
reply for A2
>Question 1 points out that suppression of miR-541 expression is related to epigenetic silencing.
If so, it is possible that similar results could be obtained with the cells that make up the liver, such
as hepatocytes, cylinder-like endothelial cells, and hepatic stellate cells. Similar suppression of
expression may also be observed in tissues other than liver tissues. I understand that you can't
analyze it because you don't have the materials, but please provide your opinion by including
the existing information.
reply for A5
>Related to Q1's comment earlier, please indicate at what point in fibrosis the Notch signal is
activated and whether this reaction is reversible.
LX2 cells become activated when TGF# is applied, and once activated, TGF# is removed and
the LX2 cells become quiescent again.
Why not consider how this phenomenon that the author points out changes using such an
experimental system?
reply for A7
>The importance of treatment for liver fibrosis differs depending on the state of mild liver
fibrosis and the state of liver cirrhosis. Furthermore, if liver fibrosis is mild, treatment response
can be expected, but otherwise it is expected to be difficult to obtain promising results. From
this point of view as well, in order to demonstrate the usefulness of gene therapy using miR-541,
it is extremely important to show that the miR-541/JAG2 axis that I discovered indicates which
phase of liver fibrosis is occurring.
There are no additional comments for comments A3, A4, and A6.
Please review this paper.
user
Title: miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to
inhibit the activation of hepatic stellate cells
Version: 3 Date: 31 Dec 2023
Reviewer's report:
Comment to author
reply for A1
>When is epigenetic downregulation likely to occur? This is the period when liver damage
occurs due to viruses or alcohol (acute phase), or when liver fibrosis occurs and liver
sinusoidal cells become capillary and become hypoxic, or even when extracellular matrix causes
pathological histopathology. Has liver fibrosis been confirmed?
Please give your opinion on this. This is related to the answer to Q5 that I commented on last
time.
Is it possible that we are seeing epigenetic silencing of miR-541 as a negative feedback after
liver fibrosis?
reply for A2
>Question 1 points out that suppression of miR-541 expression is related to epigenetic silencing.
If so, it is possible that similar results could be obtained with the cells that make up the liver, such
as hepatocytes, cylinder-like endothelial cells, and hepatic stellate cells. Similar suppression of
expression may also be observed in tissues other than liver tissues. I understand that you can't
analyze it because you don't have the materials, but please provide your opinion by including
the existing information.
reply for A5
>Related to Q1's comment earlier, please indicate at what point in fibrosis the Notch signal is
activated and whether this reaction is reversible.
LX2 cells become activated when TGF# is applied, and once activated, TGF# is removed and
the LX2 cells become quiescent again.
Why not consider how this phenomenon that the author points out changes using such an
experimental system?
reply for A7
>The importance of treatment for liver fibrosis differs depending on the state of mild liver
fibrosis and the state of liver cirrhosis. Furthermore, if liver fibrosis is mild, treatment response
can be expected, but otherwise it is expected to be difficult to obtain promising results. From
this point of view as well, in order to demonstrate the usefulness of gene therapy using miR-541,
it is extremely important to show that the miR-541/JAG2 axis that I discovered indicates which
phase of liver fibrosis is occurring.
There are no additional comments for comments A3, A4, and A6.
assistant