New insight into reactive ductular cells of biliary atresia provided by pathological assessment of SOX9
New insight into reactive ductular cells of biliary atresia provided by pathological assessment of SOX9
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DOI：
10.1007/s00383-014-3497-7
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发表时间：
2014-03
影响因子：
1.8
通讯作者：
H. Suda;D. Yoshii;Kenichiro Yamamura;Y. Yokouchi;Y. Inomata
中科院分区：
文献类型：
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作者：
H. Suda;D. Yoshii;Kenichiro Yamamura;Y. Yokouchi;Y. Inomata
背景胆道闭锁（BA）患者经有效的加塞术（KP）后可存活至青春期。如果肝纤维化进展，即使成功的KP，肝移植（LTx）是不可避免的。阐明其原因和病理生理学将打开治疗这些患者的非侵入性管理的可能性。SOX 9是一种调节胆管发育并促进肝再生和纤维化的转录因子。为了阐明SOX 9在BA肝中的作用，我们研究了SOX 9的表达patterns. MethodsImmunostaining与抗SOX 9抗体在KP或LTx时获得的肝标本。我们分析了SOX9的表达与临床data.ResultsIn BA肝脏，SOX9的反应性小管细胞（RDCs），主要是与核占主导地位的模式。SOX 9也异位表达在肝细胞，这是更明显的时间比LTx的KP。结论SOX9可能通过影响RDC和肝细胞参与了BA患者RDC的形成。SOX 9可能是理解RDC形成机制的关键分子，这一理解将为有效治疗BA提供治疗策略。
BackgroundBiliary atresia (BA) patients may survive until adolescence after effective Kasai procedure (KP). If liver fibrosis progresses even after successful KP, liver transplantation (LTx) is inevitable. Elucidation of its cause and pathophysiology would open the possibility of treating these patients by non-invasive management. SOX9 is a transcription factor that regulates bile duct development and contributes to liver regeneration and fibrosis. To elucidate the role of SOX9 in BA liver, we investigated the SOX9 expression pattern.MethodImmunostaining with anti-SOX9 antibody was done on hepatic specimens obtained at the time of KP or LTx. We analyzed the association of SOX9 expression with clinical data.ResultsIn BA livers, SOX9 was expressed in reactive ductular cells (RDCs), mostly with a nuclear-dominant pattern. SOX9 was also ectopically expressed in hepatocytes, which was more conspicuous at the timing of KP than LTx. SOX9 expression level was significantly correlated with age (days) at which KP was performed, AST and WBC count.ConclusionsSOX9 may contribute to RDC formation in BA patients, by affecting both RDCs and hepatocytes. SOX9 could be a key molecule to understand the mechanism of RDC formation, and this understanding would provide a therapeutic strategy for effective treatment of BA.