SOX9 positive biphenotypic cell mediate ductular reaction with Notch signaling in Biliary atresia

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Kumamoto University
• Principal Investigator: Inomata Yukihiro 熊本大学, その他の研究科, 教授 (50193628)
• Co-Investigator(Kenkyū-buntansha): SUDA HIROKO 熊本大学, 医学部附属病院, 非常勤診療医師 (40632659) ; YOKOUCHI YUJI 福島県立医科大学, 医学部, 教授 (60252227) ; SAKAMOTO SEISUKE 熊本大学, 医学部附属病院, 非常勤診療医師 (00378689)
• Research Collaborator: YOSHII DAIKI 熊本大学, 医学部附属病院, 大学院生
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 胆道閉鎖症 / SOX9遺伝子 / 細胆管反応 / 葛西手術 / 胆汁うったい

Outline of Final Research Achievements

The mechanism of ductular reaction (DR) seen in liver diseases including biliary atresia (BA) has been still controversial. Notch signaling has been reported to involve in biliary development and differentiation in vivo. The aim was to elucidate the role of SOX9+ biphenotypic cells in DR and the association between Notch signaling and development of DR. Formalin fixed paraffin embedded liver sections from 47 liver specimens with BA were used. Image processing was performed by Image J 1.46 software after immunofluorescence staining. Sustained or progressive cholestasis led to decreasing of SOX9+HepPar1+ ratio and increasing CK19+ ratio, whereas reduction of jaundice led to increasing of SOX9+HepPar1+ ratio and decreasing CK19+ ratio. SOX9+HepPar1+ ratio had significant negative correlation with CK19+ ratio (r = -0.6, p = 0.002). In conclusion, DR in BA is　mediated by SOX9+ biphenotypic cells, and Notch signaling is presumably required for development of DR.

Free Research Field

小児外科学