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Research
Zi Li
Sino-French Hoffmann Institute
Corresponding Author
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Background: The hepatic stellate cells (HSCs) activation plays pivotal role in hepatic inflammation and liver fibrosis.TLR4 pathway activation has been reported to be involved in mice liver fibrosis induced by hepatitis virus infection, alcohol abuse, biliary ligation, carbon tetrachloride 4 treatment and Schistosoma japonicum (Sj) infection. The effect and mechanisms of cyclooxygenase 2 (COX2)/prostanoid E2 (PGE2) axis on liver fibrosis induced by Sj are still unclear.
Results: This study investigated the link between COX2/PGE2 axis and TLR4 signaling in the induction of liver fibrogenesis in mice during Sj infection and in vitro culturing hepatic stellate cells (HSCs) strain-LX-2. The COX2/PGE2 axis was positively related with Sj-induced liver fibrosis. TLR4 pathway activation stimulated the COX2/PGE2 axis, in Sj-infected mice andin lipopolysaccharide (LPS)-exposed cultured HSCs. Synthetic PGE2 activated culturing HSCs through up-regulating alpha smooth muscle actin (α-SMA) expression. In LPS-triggered HSCs, NS398, a COX2 inhibitor led to suppression of PGE2 synthesis and reduced expression of α-SMA and type I collagen (COL I).
Conclusions: These results indicated firstly the positive association of COX2/PGE2 axis with liver fibrosis induced by Sj infection. TLR4 signaling may control COX2/PGE2 axis in Sj-infected mice liver and in vitro culturing HSCs at least partially. COX2/PGE2-EP2/EP4 axis might be good drug targets against liver fibrosis induced by Sj infection.
Keywords
TLR4 signaling, COX2/PGE2 axis, liver fibrosis, Schistosoma japonicum
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CURRENT STATUS: Under Review
Version (no preprint)
Posted 30 Mar, 2021
Review #3 received
Received 30 Mar, 2021
Editorial decision: Minor Revision
On 30 Mar, 2021
Review #2 received
Received 28 Mar, 2021
Review #1 received
Received 28 Mar, 2021
Reviewer #3 agreed
On 23 Mar, 2021
Reviewer #2 agreed
On 22 Mar, 2021
Reviewers invited
Invitations sent on 21 Mar, 2021
Reviewer #1 agreed
On 21 Mar, 2021
Editor assigned
On 03 Mar, 2021
Submission checks complete
On 03 Mar, 2021
Editor invited
On 03 Mar, 2021
This version was not preprinted
Version 1
Posted 06 Jan, 2021
No community comments so far
Review #1 received
Received 03 Feb, 2021
Editorial decision: Major Revision
On 03 Feb, 2021
Reviewer #1 agreed
On 17 Jan, 2021
Reviewers invited
Invitations sent on 06 Jan, 2021
First submitted
On 30 Dec, 2020
Editor invited
On 30 Dec, 2020
Editor assigned
On 30 Dec, 2020
Submission checks complete
On 30 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Parasitology
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This preprint is under consideration at Parasites & Vectors. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Zi Li
Sino-French Hoffmann Institute
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version (no preprint)
Posted 30 Mar, 2021
Review #3 received
Received 30 Mar, 2021
Editorial decision: Minor Revision
On 30 Mar, 2021
Review #2 received
Received 28 Mar, 2021
Review #1 received
Received 28 Mar, 2021
Reviewer #3 agreed
On 23 Mar, 2021
Reviewer #2 agreed
On 22 Mar, 2021
Reviewers invited
Invitations sent on 21 Mar, 2021
Reviewer #1 agreed
On 21 Mar, 2021
Editor assigned
On 03 Mar, 2021
Submission checks complete
On 03 Mar, 2021
Editor invited
On 03 Mar, 2021
This version was not preprinted
Version 1
Posted 06 Jan, 2021
No community comments so far
Review #1 received
Received 03 Feb, 2021
Editorial decision: Major Revision
On 03 Feb, 2021
Reviewer #1 agreed
On 17 Jan, 2021
Reviewers invited
Invitations sent on 06 Jan, 2021
First submitted
On 30 Dec, 2020
Editor invited
On 30 Dec, 2020
Editor assigned
On 30 Dec, 2020
Submission checks complete
On 30 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Parasitology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The hepatic stellate cells (HSCs) activation plays pivotal role in hepatic inflammation and liver fibrosis.TLR4 pathway activation has been reported to be involved in mice liver fibrosis induced by hepatitis virus infection, alcohol abuse, biliary ligation, carbon tetrachloride 4 treatment and Schistosoma japonicum (Sj) infection. The effect and mechanisms of cyclooxygenase 2 (COX2)/prostanoid E2 (PGE2) axis on liver fibrosis induced by Sj are still unclear.
Results: This study investigated the link between COX2/PGE2 axis and TLR4 signaling in the induction of liver fibrogenesis in mice during Sj infection and in vitro culturing hepatic stellate cells (HSCs) strain-LX-2. The COX2/PGE2 axis was positively related with Sj-induced liver fibrosis. TLR4 pathway activation stimulated the COX2/PGE2 axis, in Sj-infected mice andin lipopolysaccharide (LPS)-exposed cultured HSCs. Synthetic PGE2 activated culturing HSCs through up-regulating alpha smooth muscle actin (α-SMA) expression. In LPS-triggered HSCs, NS398, a COX2 inhibitor led to suppression of PGE2 synthesis and reduced expression of α-SMA and type I collagen (COL I).
Conclusions: These results indicated firstly the positive association of COX2/PGE2 axis with liver fibrosis induced by Sj infection. TLR4 signaling may control COX2/PGE2 axis in Sj-infected mice liver and in vitro culturing HSCs at least partially. COX2/PGE2-EP2/EP4 axis might be good drug targets against liver fibrosis induced by Sj infection.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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