Objective: Fenestrations are pores in the liver sinusoidal endothelium that facilitate the transfer of particulate substrates between the sinusoidal lumen and hepatocytes. Fenestrations express caveolin-1 and have structural similarities to caveolae, therefore might be a form of caveolae and caveolin-1 may be integral to fenestration structure and function. Therefore, fenestrations were studied in the livers of caveolin-1 knockout mice.
Methods: Scanning, transmission and immunogold electron microscopic techniques were used to study the liver sinusoidal endothelium and other tissues in caveolin-1 knockout and wild-type mice.
Results: Comparison of fenestrations in wild-type and knockout mice did not reveal any differences on either scanning or transmission electron microscopy. The diameter of the fenestrations was not significantly different (74 +/- 13 nm knockout mice vs 78 +/- 12 nm wild-type mice) nor was the fenestration porosity (6.5 +/- 2.1 knockout vs 7.3 +/- 2.4% wild-type mice). In contrast, adipocytes and blood vessels in other tissues lacked caveolae in the knockout mice. Caveolin-1 immunogold of livers of wild-type mice indicated sparse expression in sinusoidal endothelial cells.
Conclusions: The normal structure of fenestrations in the liver sinusoidal endothelium is not dependent upon caveolin-1 and fenestrations are not a form of caveolae.
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http://dx.doi.org/10.1111/j.1549-8719.2009.00004.x | DOI Listing |
Liver Int
February 2025
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Background And Aims: Porto-sinusoidal vascular disorder (PSVD) is a rare vascular liver disorder characterised by specific histological findings in the absence of cirrhosis, which is poorly understood in terms of pathophysiology. While elevated hepatic copper content serves as diagnostic hallmark in Wilson disease (WD), hepatic copper content has not yet been investigated in PSVD.
Methods: Patients with a verified diagnosis of PSVD at the Medical University of Vienna and available hepatic copper content at the time of diagnosis of PSVD were retrospectively included.
Biomed Pharmacother
January 2025
Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium; Liver Research Center Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium. Electronic address:
Portal hypertension (PH) can cause severe complications in patients with advanced chronic liver disease (aCLD). The pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor reduces portal pressure in preclinical models of aCLD. Since the effect on PH might be secondary to fibrosis improvement, we investigated the effect of lanifibranor on PH, hepatic and splanchnic angiogenesis in mouse models of fibrotic and prehepatic non-fibrotic PH.
View Article and Find Full Text PDFSTAR Protoc
January 2025
Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address:
Liver sinusoidal endothelial cells (LSECs) line the liver sinusoids and play a crucial role in liver function. Isolating LSECs is beneficial for their functional evaluation in vitro. Here, we provide a protocol for obtaining purified LSECs from mice via gradient centrifugation and magnetic cell sorting (MACS), yielding cells suitable for culture and downstream analyses.
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 PDFExpert Opin Drug Metab Toxicol
January 2025
Institut de R&D Servier, Paris-Saclay, F-91190 Gif-sur-Yvette, France.
Introduction: Drug-mediated inhibition of bile salt efflux transporters may cause liver injury. In vitro prediction of drug effects toward canalicular and/or sinusoidal efflux of bile salts from human hepatocytes is therefore a major issue, which can be addressed using liver cell-based assays.
Area Covered: This review, based on a thorough literature search in the scientific databases PubMed and Web of Science, provides key information about hepatic transporters implicated in bile salt efflux, the human liver cell models available for investigating functional inhibition of bile salt efflux, the different methodologies used for this purpose, and the modes of expression of the results.
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