As a newly identified partner in the TGF-β activation network that is specifically expressed selleck chemicals in HSCs during chronic liver injury, we propose that ADAMTS1 is a key player in the dynamic interplay that helps regulate TGF-β activity. The authors thank the Rennes Biological Resources Center (CHRU Pontchaillou, IFR 140) for its contribution to human tissue sampling. We acknowledge the excellent support of the Nice-Sophia Antipolis Transcriptome Platform
of the Marseille-Nice Genopole, in which the microarray experiments were carried out. Special thanks are due to Virginie Magnone and Géraldine Rios for microarray production. The authors thank Dr. J.E. Murphy-Ullrich (University of Alabama at Birmingham, Birmingham, AL) and Dr. D. Cataldo (University of Liège, Liège, Belgium) for providing the LAP-TGF-β and ADAMTS1 constructs, respectively. The authors thank Dr. M. Baudy-Floc’h (University of Rennes, ICMV, UMR CNRS 6226, Rennes, France) for peptide synthesis, Dr. C. Piquet-Pellorce (University of Rennes, SeRAIC EA4427) for animal experimentation, Dr. C. Lucas (Service Biochimie, CHU Rennes) for enzyme measurements,
and Dr. E. Schaub for SHG analyses (PIXEL facilities, University of Rennes 1). The authors thank selleck inhibitor Dr. E. Käs (LBME, CNRS/Université Paul Sabatier) for useful discussions and a critical reading of the manuscript. Additional Supporting Information may be found in the online version of this article. “
“Background and
Aim: Inflammation plays a pivotal role in liver injury. Gabexate mesilate (GM, a protease inhibitor) inhibits inflammation by blocking various serine proteases. This study examined tuclazepam the effects of GM on hepatic encephalopathy in rats with acute and chronic liver failure. Methods: Acute and chronic liver failure (cirrhosis) were induced by intraperitoneal TAA administration (350 mg/kg/day for 3 days) and common bile duct ligation, respectively, in male Sprague-Dawley rats. Rats were randomized to receive either GM (50 mg/10 mL/kg) or saline intraperitoneally for 5 days. Severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters, mean arterial pressure and portal pressure, were measured (only in chronic liver failure rats). Plasma levels of liver biochemistry, ammonia, nitrate/nitrite, interleukins (IL) and tumor necrosis factor (TNF)-α were determined. Results: In rats with acute liver failure, GM treatment significantly decreased the plasma levels of alanine aminotransferase (P = 0.02), but no significant difference of motor activity, plasma levels of ammonia, IL-1β, IL-6, IL-10 and TNF-α or survival was found. In chronic liver failure rats, GM significantly lowered the plasma TNF-α levels (P = 0.04). However, there was no significant difference of motor activity, other biochemical tests or survival found. GM-treated chronic liver failure rats had higher portal pressure (P = 0.