Aim: To determine platelet activating factor (PAF) receptor expression in cirrhotic hepatic stellate cells.
Methods: Hepatic stellate cells, isolated from the livers of control and CCl(4)-induced cirrhotic rats, were placed in serum-free medium after overnight culture. We determined the PAF receptor in hepatic stellate cells by saturation binding technique and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and the effects of PAF and its antagonist BN52021 on prostaglandin E(2) (PGE(2)) release by stellate cells.
Results: Scatchard analysis indicated the presence of PAF receptor with dissociation constant (Kd) of 4.66 nmol/L and maximum binding capacity (Bmax) of 24.65 fmol/microg in cirrhotic stellate cells. Compared with the control, the maximum PAF binding capacity increased significantly (Bmax: 24.65 +/- 1.96 fmol/microg. DNA, R = 0.982 vs 5.74 +/- 1.55 fmol/microg. DNA, R = 0.93; P < 0.01), whereas receptor affinity had no significant difference (Kd of 4.66 +/- 0.33 nmol/L for the cirrhosis and 3.51 +/- 0.26 nmol/L for the control; P > 0.05). Consistent with the receptor binding data, the mRNA expression of PAF receptor was increased significantly in cirrhotic stellate cells. PAF in a concentration-dependent manner induced PGE(2) synthesis in cirrhotic hepatic stellate cells, but the effects were blocked significantly by BN52021.
Conclusion: Cirrhosis sensitizes hepatic stellate cells to PAF by elevating its receptor level and hepatic stellate cells maybe potential effectors of PAF induced portal hypertension.
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http://dx.doi.org/10.3748/wjg.14.218 | DOI Listing |
Eur J Pharmacol
January 2025
College of Korean Medicine, Gachon University, Seongnam 13120, Korea. Electronic address:
Obesity due to excessive body fat accumulation remains a global problem. Patients with obesity have high cortisol levels, and its dysregulation is caused by increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) levels. The effects and mechanism of J2H-1702, an 11β-HSD1 inhibitor, on nonalcoholic steatohepatitis (NASH) were explored.
View Article and Find Full Text PDFJ Colloid Interface Sci
January 2025
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China. Electronic address:
Liver fibrosis is a common pathological stage in the development of several chronic liver diseases, and early intervention can effectively reverse the developing process. Excessive reactive oxygen species (ROS) can promote the activation of hepatic stellate cells (HSCs), but existing treatments have not addressed this problem. In this study, different metal-based mesoporous polydopamine (MPDA) was prepared by the soft template method, and their free radical scavenging abilities, as well as the efficacy and safety of the carriers were investigated, so as to select Cu-coordinated MPDA (CMP) as the optimal nanocarrier.
View Article and Find Full Text PDFLiver Int
February 2025
Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Background And Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterised by progressive biliary inflammation and fibrosis, leading to liver cirrhosis and cholangiocarcinoma. GPBAR1 (TGR5) is a G protein-coupled receptor for secondary bile acids. In this study, we have examined the therapeutic potential of BAR501, a selective GPBAR1 agonist in a PSC model.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P.R. China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P.R. China.
Ethnopharmacological Relevance: Liver fibrosis, which is a precursor to cirrhosis in chronic liver diseases, is driven by various factors. The activation and proliferation of hepatic stellate cells (HSCs) are recognized as a crucial phase in the progression of liver fibrosis. Compared with western drug therapy, Traditional Chinese medicine (TCM) and herbal medicine not only have the advantages of multi-target and multi-pathways in the treatment of liver fibrosis, but also have high safety without toxic side effects.
View Article and Find Full Text PDFPhytomedicine
January 2025
Department of Gastroenterology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. Electronic address:
Background: Celastrol was recently identified as a potential treatment for obesity and hepatic steatosis. However, whether Celastrol effectively suppresses the nonalcoholic fatty liver disease (NAFLD) stage remains unknown. This study aimed to evaluate the role of Celastrol in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis.
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