Down‐regulation of hepatocyte nuclear factor‐4α and defective zonation in livers expressing mutant Z α1‐antitrypsin

• DOI: 10.1002/hep.29160
• Publication Date: 2017-03-15T08:43:09Z
• Authors: Pasquale Piccolo; Patrizia Annunziata; Leandro R. Soria; Sergio Attanasio; Anna Barbato; Raffaele Castello; Annamaria Carissimo; Luca Quagliata; Luigi M. Terracciano; Nicola Brunetti‐P...
• Keywords: Hepatocyte nuclear factors; Liver disease

α 1 ‐Antitrypsin (AAT) deficiency is one of the most common genetic disorders and liver disease due to Z mutant AAT (ATZ) a prototype conformational disorder protein misfolding with consequent aberrant intermolecular aggregation. In present study, we found that livers PiZ transgenic mice expressing human ATZ have altered expression network hepatocyte transcriptional factors, including nuclear factor‐4α, early down‐regulated induces repression expression. Reduced factor‐4α was associated activation β‐catenin, which regulates zonation. Livers patients were both severe perturbation Functionally, showed defect ureagenesis, as shown by increased baseline ammonia, reduced urea production survival after an ammonia challenge. Down‐regulation defective zonation in not been recognized so far features caused are likely involved metabolic disturbances risk hepatocellular carcinoma deficiency. Conclusion : The findings this study consistent concept abnormal conformation intrahepatic accumulation broad effects on functions. (H epatology 2017;66:124–135).