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.
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Posted 06 Jan, 2021
Received 03 Feb, 2021
On 03 Feb, 2021
On 17 Jan, 2021
Invitations sent on 06 Jan, 2021
On 30 Dec, 2020
On 30 Dec, 2020
On 30 Dec, 2020
On 30 Dec, 2020
Posted 06 Jan, 2021
Received 03 Feb, 2021
On 03 Feb, 2021
On 17 Jan, 2021
Invitations sent on 06 Jan, 2021
On 30 Dec, 2020
On 30 Dec, 2020
On 30 Dec, 2020
On 30 Dec, 2020
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
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