Background: Hepatic stellate cell (HSC) activation plays a 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 the cyclooxygenase 2 (COX2)/prostanoid E2 (PGE2) axis on liver fibrosis induced by Sj are still unclear.
Methods: Mice liver fibrosis were induced by cutaneous infection of Sj cercariae. COX-2 inhibitor, NS398 were injected from week 5 to week 7, while TLR4 inhibitor TAK242 were injected from week 4 to week 8 post Sj infection. Human HSCs line, LX-2 cells were cultured and exposed to LPS or synthetic PGE2, or pretreated by TAK242, TLR4-siRNA or NS398. Liver tissue and serum or in vitro cultured cell lysaste were collected at indicated time courses for exploring the relationship between TLR4 and COX2-PGE2 axis through qPCR, western blot, immunohistochemical assay, ect. One-way analysis of variance among multiple groups followed by Uncorrected Fisher's LSD-t test or paired comparisons through t test were performed to tell the statistical differences.
Results: This study investigated the link between the COX2/PGE2 axis and TLR4 signaling in the induction of liver fibrogenesis in mice during Sj infection and in vitro culture of HSC strain-LX-2. The COX2/PGE2 axis was positively associated with Sj-induced liver fibrosis. TLR4 pathway activation stimulated the COX2/PGE2 axis in Sj-infected mice and in lipopolysaccharide (LPS)-exposed cultured HSCs. Synthetic PGE2 activated cultured HSCs through upregulation of 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 indicate firstly the positive association of the COX2/PGE2 axis with liver fibrosis induced by Sj infection. TLR4 signaling may at least partially control the COX2/PGE2 axis in Sj-infected mice liver and in vitro cultured HSCs. The COX2/PGE2-EP2/EP4 axis might be a good drug target against liver fibrosis induced by Sj infection.
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http://dx.doi.org/10.1186/s13071-021-04790-7 | DOI Listing |
Anal Chem
January 2025
Research Unit of Environmental Toxicology, School of Public Health, China Medical University, Shenyang 110122, China.
Although cathepsin S is transported from the spleen to the liver, where it cleaves collagen XVIII to produce endostatin and plays a critical role in the onset of early liver fibrosis, the relationship between liver fibrosis and spleen function remains underexplored. Given the roles of phosphorylation in disease, understanding its regulatory mechanism in early liver fibrosis is crucial. Despite advances in mass spectrometry enhancing phosphoproteomics, its application is limited by small clinical samples and subtle protein changes.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health, South Limburg Public Health Service, Heerlen, The Netherlands.
Undetected chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections can lead to cirrhosis and liver cancer. Syrian migrants are the largest non-European migrant group in the Netherlands with HBV and HCV prevalence rates above 2%. This study aimed to reach Syrian migrants for HBV and HCV testing using point-of-care tests (POCT).
View Article and Find Full Text PDFLiver Int
February 2025
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Endocr Oncol
January 2024
OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK.
Current models for the study of neuroendocrine tumours (NETs) are severely limited. While (e.g.
View Article and Find Full Text PDFJ Clin Exp Hepatol
November 2024
Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
Background: There are limited studies assessing whether prophylactic platelet transfusions prior to high-risk procedures reduce the risk of bleeding in patients with liver cirrhosis.
Methods: We performed a analysis of two prior randomized clinical trials (CTRI/2017/12/010822 and CTRI/2021/05/033464), which compared thromboelastography-guided prophylactic platelet transfusion to standard-of-care (empirical prophylactic transfusion for all patients prior to the procedure) or on-demand transfusion (no prophylactic transfusions). We aimed to assess the risk of major procedure-related bleeding or mortality among patients who had received prophylactic platelet transfusions versus those who did not (on-demand transfusions).
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