Gallbladder wall abnormality in biliary atresia of mouse Sox17+/- neonates and human infants

Mami Uemura, Mayumi Higashi, Montri Pattarapanawan, Shohei Takami, Naoki Ichikawa, Hiroki Higashiyama, Taizo Furukawa, Jun Fujishiro, Yuki Fukumura, Takashi Yao, Tatsuro Tajiri, Masami Kanai-Azuma, Yoshiakira Kanai

研究成果: Contribution to journalArticle査読

5 被引用数 (Scopus)


Biliary atresia (BA) is characterized by the inflammation and obstruction of the extrahepatic bile ducts (EHBDs) in newborn infants. SOX17 is a master regulator of fetal EHBD formation. In mouse Sox17+/- BA models, SOX17 reduction causes cell-autonomous epithelial shedding together with the ectopic appearance of SOX9-positive cystic duct-like epithelia in the gallbladder walls, resulting in BA-like symptoms during the perinatal period. However, the similarities with human BA gallbladders are still unclear. In the present study, we conducted phenotypic analysis of Sox17+/- BA neonate mice, in order to compare with the gallbladder wall phenotype of human BA infants. The most characteristic phenotype of the Sox17+/- BA gallbladders is the ectopic appearance of SOX9-positive peribiliary glands (PBGs), so-called pseudopyloric glands (PPGs). Next, we examined SOX17/SOX9 expression profiles of human gallbladders in 13 BA infants. Among them, five BA cases showed a loss or drastic reduction of SOX17-positive signals throughout the whole region of gallbladder epithelia (SOX17-low group). Even in the remaining eight gallbladders (SOX17-high group), the epithelial cells near the decidual sites were frequently reduced in the SOX17-positive signal intensity. Most interestingly, the most characteristic phenotype of human BA gallbladders is the increased density of PBG/PPG-like glands in the gallbladder body, especially near the epithelial decidual site, indicating that PBG/PPG formation is a common phenotype between human BA and mouse Sox17+/- BA gallbladders. These findings provide the first evidence of the potential contribution of SOX17 reduction and PBG/PPG formation to the early pathogenesis of human BA gallbladders.

ジャーナルDMM Disease Models and Mechanisms
出版ステータス出版済み - 4 2020

All Science Journal Classification (ASJC) codes

  • 神経科学(その他)
  • 医学(その他)
  • 免疫学および微生物学(その他)
  • 生化学、遺伝学、分子生物学(全般)


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