Biliary type liver fibrosis develops as part of the wound healing response to bile duct injury in chronic cholestatic liver diseases. The origin of myofibroblasts accumulating together with extracellular matrix around proliferating bile duct structures (referred to as ductular reaction) in the setting of cholestatic injury, has been investigated mostly in the rat bile duct ligation model. Evide...

There is a need for new noninvasive biomarkers (NIBMs) able to assess cholestasis and fibrosis in chronic cholestatic liver diseases (CCLDs). Tumorigenesis can arise from CCLDs. Therefore, autoantibodies to tumor-associated antigens (TAA) may be early produced in response to abnormal self-antigen expression caused by cholestatic injury. Vascular endothelial growth factor receptor-3 (VEGFR-3) ha...

Interleukin (IL)-10 expression is induced in activated hepatic stellate cells (HSC) in vitro and in vivo. We analyzed expression of IL-10 receptor (IL-10R) and coreceptor cytokine receptor family (CRF2-4) in HSC. We aimed to clone and sequence partial cDNA for rat IL-10R and CRF2-4, determine their expression in activated rat HSC in vivo and in vitro, and examine the biological responsiveness o...

In cholestatic liver diseases, bile acids induce hepatocyte apoptosis and thus cause liver injury, but hepatic stellate cells (HSCs) survive in the presence of bile acids. We attempted to analyze anti-apoptotic signaling pathways in HSCs against bile acid-induced apoptosis. In immortalized human HSCs and primarily cultured rat HSCs, bile acid treatment increased the expression levels of cycloox...

Cholestatic liver disease is characterized by the progressive destruction of biliary epithelial cells (BECs) followed by fibrosis, cirrhosis and liver failure. Activated hepatic stellate cells (HSCs) and portal fibroblasts are the major cellular effectors of enhanced collagen deposition in biliary fibrosis. Apamin, an 18 amino acid peptide neurotoxin found in apitoxin (bee venom), is known to b...

Intrahepatic bile acid accumulation due to inhibition of the bile salt export pump (BSEP) has been proposed as a mechanism for drug-induced cholestasis. Many cholestatic drugs do not initiate hepatotoxicity in rats, although they inhibit rat Bsep and cause elevated serum bile acid concentration. In this study, we examined changes in the taurocholate (TC) transport in response to cholestatic dru...

The effects of extrahepatic cholestasis upon adrenergic regulation of glycogenolysis and upon the numbers of adrenoceptors in rat liver were studied using isolated hepatocytes and plasma membranes, respectively. A 60% decrease in the number of alpha 1 adrenoceptors (285 vs. 680 fmol/mg protein) and a simultaneous 2.7-fold increase in the number of beta adrenergic sites (67 vs. 25 fmol/mg protei...