ETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis.
ETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis.
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DOI：
10.1002/dvdy.24626
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Rustgi AK
中科院分区：
文献类型：
--
作者：
Das KK;Heeg S;Pitarresi JR;Reichert M;Bakir B;Takano S;Kopp JL;Wahl-Feuerstein A;Hicks P;Sander M;Rustgi AK
胰腺腺泡细胞经历腺泡到导管化生（ADM）的可塑性已被证明有助于胰腺损伤后的再生。Sox 9对于导管细胞的命运是关键的，并且在ADM的形成中是重要的，最有可能与尚未完全阐明的转录因子的复杂层次一致。利用小鼠急性胰腺炎模型和原代胰腺导管细胞的三维类器官培养，我们在此描述Ets-转录因子Etv 5作为导管细胞身份和ADM的关键调节因子，其作用于Sox 9的上游并且对于ADM中的Sox 9表达是必需的。Etv 5的缺失与急性胰腺炎的严重程度增加和ADM形成受损相关，从而导致组织再生延迟，回复受伤的回复。我们的数据提供了新的见解，在我们的胰腺稳态，胰腺炎和上皮可塑性的理解与ADM的调节。
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. Utilizing 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. Our data provide new insights in the regulation of ADM with implications in our understanding of pancreatic homeostasis, pancreatitis and epithelial plasticity.
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影响因子：
23.9
作者：
Puri, Sapna;Folias, Alexandra E.;Hebrok, Matthias
通讯作者：
Hebrok, Matthias
影响因子：
5.3
作者：
Jacquemin, P;Durviaux, SM;Lemaigre, FP
通讯作者：
Lemaigre, FP
DOI：
10.1073/pnas.0405776102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Haumaitre, C;Barbacci, E;Cereghini, S
通讯作者：
Cereghini, S
影响因子：
29.4
作者：
Gruber R;Panayiotou R;Nye E;Spencer-Dene B;Stamp G;Behrens A
通讯作者：
Behrens A
影响因子：
29.4
作者：
Heeg S;Das KK;Reichert M;Bakir B;Takano S;Caspers J;Aiello NM;Wu K;Neesse A;Maitra A;Iacobuzio-Donahue CA;Hicks P;Rustgi AK
通讯作者：
Rustgi AK