Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells
作者： Fabián Arenas , Isabel Hervias , Miriam Úriz , Ruth Joplin , Jesús Prieto
DOI: 10.1172/JCI33156
关键词:
摘要: Primary biliary cirrhosis (PBC) is a cholestatic disease associated with autoimmune phenomena and alterations in both bicarbonate excretion expression of the carrier AE2. The bile acid ursodeoxycholic (UCDA) currently used treatment liver diseases choice PBC; however, subset PBC patients respond poorly to UDCA monotherapy. In these patients, combination glucocorticoid therapy appears be beneficial. To address mechanism this benefit, we analyzed effects dexamethasone on AE2 gene human cells from hepatocyte cholangiocyte lineages. dexamethasone, but not or alone, increased liver-enriched alternative mRNA isoforms AE2b1 AE2b2 enhanced activity. Similar were obtained after replacing conjugates. vitro vivo reporter assays, found that UDCA/dexamethasone upregulated alternate overlapping promoter sequences which are expressed. chromatin immunoprecipitation demonstrated UCDA/dexamethasone induced p300-related interactions between HNF1 receptor promoter. Our data provide potential molecular explanation for beneficial glucocorticoids inadequate response
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