The analysis for the etiology and pathogenesis of Biliary atresia using a Sox9 conditional knockout mouse

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861672
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Kumamoto University
• Principal Investigator: SUDA Hiroko 熊本大学, 医学部附属病院, 非常勤診療医師 (40632659)
• Research Collaborator: YOSHII Daiki 熊本大学, 医学部附属病院
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 胆道閉鎖症 / Sox9

Outline of Final Research Achievements

Biliary atresia (BA) is a rare infantile disease characterized by bile duct obliteration with the pathogenesis unknown. Ductular reaction (DR) is one of the characteristic features of BA. We focused on Sex-determining Region Y-box9 (SOX9), which is a crucial transcription factor that regulates bile duct development and liver damage/regeneration. The aims of this study are to investigate the role of SOX9 in liver injury and DR. Experiments using Sox9 knockout (KO) mouse showed that the level of alanine aminotransferase (ALT) of Sox9 KO mouse was significantly higher than that of control mouse in CCL4 treatment. Experiment of the SOX9 gene transfection using hydrodynamic injection method revealed induction of Osteopontin and reduction of Hepatocyte growth factor 4 alpha (Hnf4α) in the transfected hepatocytes. These results indicated that SOX9 has a potential to involve in liver damage/regeneration and transdifferentiation of hepatocytes to cholangiocytes during progression of DR.

Free Research Field

小児外科