HMGB1 inflammosome activity modulates HIF-1α in a rat model of thioacetamide (TAA)-induced chronic liver damage and cholangiocarcinoma development

Background: HIF-1α and HIF-2α have been identified as key mediators of angiogenesis, inflammation, and metabolism and can activate simultaneously distinct target genes with different functions regarding the regulation of hypoxia-related-genes. Methods: Male Wistar rats and TLR-4-/- mice were administrated thioacetamide (TAA) in drinking water up to 20 weeks and sacrificed at 4, 8, 12, 16, 20 weeks. Expression of HIF-1α and HIF-2α was evaluated during liver damage and cholangiocarcinoma. Expression of HIF-1α, HIF-2α, HMGB1 was measured by RT-PCR and Western blot. HIF-1α, HIF-2α, α-SMA, CK-19, ED1 and ED2 were loc…