BMC Gastroenterology | VOL. 22
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Expression of unfolded protein response genes in post-transplantation liver biopsies

Publication Date Aug 10, 2022

Abstract

Abstract Background Cholestatic liver diseases are a major source of morbidity and mortality that can progress to end-stage liver disease and hyperbilirubinemia is a hallmark of cholestasis. There are few effective medical therapies for primary biliary cholangitis, primary sclerosing cholangitis and other cholestatic liver diseases, in part, due to our incomplete understanding of the pathogenesis of cholestatic liver injury. The hepatic unfolded protein response (UPR) is an adaptive cellular response to endoplasmic reticulum stress that is important in the pathogenesis of many liver diseases and recent animal studies have demonstrated the importance of the UPR in the pathogenesis of cholestatic liver injury. However, the role of the UPR in human cholestatic liver diseases is largely unknown. Methods RNA was extracted from liver biopsies from patients after liver transplantation. RNA-seq was performed to determine the transcriptional profile and hepatic UPR gene expression that is associated with liver injury and cholestasis. Results Transcriptome analysis revealed that patients with hyperbilirubinemia had enhanced expression of hepatic UPR pathways. Alternatively, liver biopsy samples from patients with acute rejection had enhanced gene expression of LAG3 and CDK1. Pearson correlation analysis of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin levels demonstrated signifi...

Concepts

Pathogenesis Of Cholestatic Liver Injury Unfolded Protein Response Unfolded Protein Response Gene Expression Hepatic Unfolded Protein Response Human Cholestatic Liver Diseases Hepatic Bile Acid Metabolism Unfolded Protein Response Gene Human Cholestatic Liver Serum Alkaline Phosphatase Levels Cholestatic Liver Injury

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