Dataset Information
Serum transferrin as a biomarker of hepatocyte nuclear factor 4 alpha activity and hepatocyte function in liver diseases.
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ABSTRACT: Background
Serum transferrin levels represent an independent predictor of mortality in patients with liver failure. Hepatocyte nuclear factor 4 alpha (HNF4?) is a master regulator of hepatocyte functions. The aim of this study was to explore whether serum transferrin reflects HNF4? activity.Methods
Factors regulating transferrin expression in alcoholic hepatitis (AH) were assessed via transcriptomic/methylomic analysis as well as chromatin immunoprecipitation coupled to DNA sequencing. The findings were corroborated in primary hepatocytes. Serum and liver samples from 40 patients with advanced liver disease of multiple etiologies were also studied.Results
In patients with advanced liver disease, serum transferrin levels correlated with hepatic transferrin expression (r?=?0.51, p?=?0.01). Immunohistochemical and biochemical tests confirmed reduced HNF4? and transferrin protein levels in individuals with cirrhosis. In AH, hepatic gene-gene correlation analysis in liver transcriptome revealed an enrichment of HNF4? signature in transferrin-correlated transcriptome while transforming growth factor beta 1 (TGF?1), tumor necrosis factor ? (TNF?), interleukin 1 beta (IL-1?), and interleukin 6 (IL-6) negatively associated with transferrin signature. A key regulatory region in transferrin promoter was hypermethylated in patients with AH. In primary hepatocytes, treatment with TGF?1 or the HNF4? inhibitor BI6015 suppressed transferrin production, while exposure to TNF?, IL-1?, and IL-6 had no effect. The correlation between hepatic HNF4A and transferrin mRNA levels was also seen in advanced liver disease.Conclusions
Serum transferrin levels constitute a prognostic and mechanistic biomarker. Consequently, they may serve as a surrogate of impaired hepatic HNF4? signaling and liver failure.
SUBMITTER: Guldiken N
PROVIDER: S-EPMC7887823 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Serum transferrin as a biomarker of hepatocyte nuclear factor 4 alpha activity and hepatocyte function in liver diseases.
BMC medicine 20210217 1
<h4>Background</h4>Serum transferrin levels represent an independent predictor of mortality in patients with liver failure. Hepatocyte nuclear factor 4 alpha (HNF4α) is a master regulator of hepatocyte functions. The aim of this study was to explore whether serum transferrin reflects HNF4α activity.<h4>Methods</h4>Factors regulating transferrin expression in alcoholic hepatitis (AH) were assessed via transcriptomic/methylomic analysis as well as chromatin immunoprecipitation coupled to DNA seque ...[more]