Necroptosis in biliary atresia of the liver

Masatoshi Hashimoto, Fumiyoshi Fujishima, Thanpisit Lomphithak, Siriporn Jitkaew, Masaki Nio, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

Abstract

Biliary atresia (BA) is characterized by the occlusion of extrahepatic bile ducts due to sclerosing inflammation. Necroptosis is a recently characterized form of programmed cell death but has not been examined in BA. We, therefore, explored the potential involvement of necroptosis in the pathogenesis of BA by evaluating the correlation between necroptosis-related factors and clinicopathological features of BA patients. We studied liver biopsy specimens of 59 patients with BA and 30 with congenital biliary dilatation (CBD). We also evaluated 14 surgical BA cases, who eventually underwent liver transplantation and 9 normal liver from neonates and infants obtained at autopsy. Necroptosis-related factors including toll-like receptor 3 (TLR3), receptor-interacting protein kinase1 (RIP1), receptor-interacting protein kinase3 (RIP3), mixed lineage kinase domain-like (MLKL), and phosphorylated mixed lineage kinase domain-like (pMLKL) in these liver specimens were immunolocalized. TLR3, RIP1, MLKL in the intrahepatic cholangiocytes was significantly higher in BA than CBD. pMLKL immunoreactivity was significantly greater at an earlier age of BA patients. The native liver survival period was significantly prolonged in the high RIP3 group. The low RIP3 status could serve as an adverse clinical prognostic factor for the native liver survival among the necroptosis-related factors examined in this study.

Original languageEnglish
JournalMedical Molecular Morphology
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Biliary atresia
  • Cell death
  • Cholangiocytes
  • Congenital biliary dilation
  • Immunohistochemistry
  • Liver
  • Necroptosis
  • Phosphorylated mixed lineage kinase domain-like

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Necroptosis in biliary atresia of the liver'. Together they form a unique fingerprint.

Cite this