ETV5通过Sox9调节导管形态发生，对胰腺炎后的再生至关重要。
ETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis.
作者信息
Das Koushik K, Heeg Steffen, Pitarresi Jason R, Reichert Maximilian, Bakir Basil, Takano Shigetsugu, Kopp Janel L, Wahl-Feuerstein Anja, Hicks Philip, Sander Maike, Rustgi Anil K
机构信息
Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
出版信息
Dev Dyn. 2018 Jun;247(6):854-866. doi: 10.1002/dvdy.24626. Epub 2018 Apr 19.
BACKGROUND
The plasticity of pancreatic acinar cells to undergo acinar to ductal metaplasia (ADM) has been demonstrated to contribute to the regeneration of the pancreas in response to injury. Sox9 is critical for ductal cell fate and important in the formation of ADM, most likely in concert with a complex hierarchy of, as yet, not fully elucidated transcription factors.
RESULTS
By using a mouse model of acute pancreatitis and three dimensional organoid culture of primary pancreatic ductal cells, we herein characterize the Ets-transcription factor Etv5 as a pivotal regulator of ductal cell identity and ADM that acts upstream of Sox9 and is essential for Sox9 expression in ADM. Loss of Etv5 is associated with increased severity of acute pancreatitis and impaired ADM formation leading to delayed tissue regeneration and recovery in response to injury.
CONCLUSIONS
Our data provide new insights in the regulation of ADM with implications in our understanding of pancreatic homeostasis, pancreatitis and epithelial plasticity. Developmental Dynamics 247:854-866, 2018. © 2018 Wiley Periodicals, Inc.
背景
胰腺腺泡细胞向腺泡-导管化生（ADM）转变的可塑性已被证明有助于胰腺在损伤后再生。Sox9对导管细胞命运至关重要，在ADM形成中起重要作用，很可能与一系列尚未完全阐明的转录因子协同作用。
结果
通过使用急性胰腺炎小鼠模型和原代胰腺导管细胞的三维类器官培养，我们在此将Ets转录因子Etv5鉴定为导管细胞特性和ADM的关键调节因子，其作用于Sox9上游，对ADM中Sox9的表达至关重要。Etv5缺失与急性胰腺炎严重程度增加和ADM形成受损有关，导致损伤后组织再生和恢复延迟。
结论
我们的数据为ADM的调控提供了新见解，对我们理解胰腺内环境稳定、胰腺炎和上皮可塑性具有重要意义。《发育动力学》247:854 - 866，2018年。©2018威利期刊公司。
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