Highlights
(from HIV coinfection exacerbates HBV-induced liver fibrogenesis through a HIF-1α- and TGF-β1-dependent pathway, from Xu et al, 2024)
HIV and HIV gp120, through engagement with coreceptors (CCR5/CXCR4), upregulate HIF-1α to increase HBV-induced TGF-β1 and profibrogenic gene expression in hepatocytes and hepatic stellate cells (HSC).
HIV coinfection increases HBV-induced liver fibrogenesis through upregulation of the HIF-1α and TGF-β1 pathway through the coreceptors.
The HIF-1α inhibitor (ACF) can block HIV, HBV and TGF-β1-induced liver fibrogenesis.
HIF-1α represents a novel target for antifibrotic therapy among patients with HIV and HBV coinfection.
Method
Human precision-cut liver slice (PCLS) ex vivo culture
All human samples were harvested under the protocols approved by the Mass General Brigham Institutional Review Boards (IRBs). PCLS from human livers were performed as published. Tissues of proper size were superglued to the vibratome mounting stage, submersed in a media chamber containing sterile Krebs Henseleit buffer (Sigma-Aldrich), and cut using a 7000smz-2 Vibratome (Campden Instruments Limited) with a 7550-1-C ceramic blade, at an advanced speed 0.1 mm/s, 2.5 mm amplitude, 50Hz frequency, and thickness of 250 μm. Slices were further tailored into the same size (5mm×5mm×250μm) using an 8-mm biopsy punch (Acuderm Inc) and were transferred into plates with 8 μm-pore Transwell inserts (Corning). All PCLS were cultured in William's E medium (Sigma-Aldrich) containing 2.0 g/L glucose, 10% fetal bovine serum, 2 mM L-glutamine supplement, 100 U/mL penicillin, and 100 μg/mL streptomycin, at 37°C in a humidified atmosphere of 5% CO2.
