Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice.
Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice.
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DOI：
10.1186/1471-2121-12-17
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发表时间：
2011-05-05
期刊：
影响因子：
--
通讯作者：
Pin CL
中科院分区：
文献类型：
--
作者：
Fazio EN;Dimattia GE;Chadi SA;Kernohan KD;Pin CL
Stanniocalcin 2 （STC2）是一种在体外内质网应激条件下由（PKR）样内质网激酶（PERK）信号激活的分泌蛋白。小鼠中STC2的过表达导致生长受限表型；然而，STC2的生理功能尚不清楚。鉴于STC2与PERK信号传导的关系，本研究的目的是研究STC2在体内PERK信号传导中的作用。由于PERK信号在胰腺中具有生理和病理作用，因此使用蛋白诱导胰腺炎（CIP）模型评估小鼠胰腺损伤前后STC2的表达。Stc2表达在胰腺损伤开始后4小时内增加，并与PERK信号激活增加相关。为了确定STC2过表达对PERK的影响，我们检测了系统表达人STC2 （STC2Tg）的小鼠。STC2Tg胰腺组织表现出正常的胰腺形态，但PERK信号激活改变，包括激活转录因子（ATF） 4积累和自噬增加。在诱导胰腺损伤后，STC2Tg小鼠表现出循环淀粉酶水平的有限增加和细胞连接的维持增加。本研究将STC2与体内PERK的病理激活联系起来，并提示STC2参与对胰腺腺泡细胞损伤的反应。
Stanniocalcin 2 (STC2) is a secreted protein activated by (PKR)-like Endoplasmic Reticulum Kinase (PERK) signalling under conditions of ER stress in vitro. Over-expression of STC2 in mice leads to a growth-restricted phenotype; however, the physiological function for STC2 has remained elusive. Given the relationship of STC2 to PERK signalling, the objective of this study was to examine the role of STC2 in PERK signalling in vivo. Since PERK signalling has both physiological and pathological roles in the pancreas, STC2 expression was assessed in mouse pancreata before and after induction of injury using a cerulein-induced pancreatitis (CIP) model. Increased Stc2 expression was identified within four hours of initiating pancreatic injury and correlated to increased activation of PERK signalling. To determine the effect of STC2 over-expression on PERK, mice systemically expressing human STC2 (STC2Tg) were examined. STC2Tg pancreatic tissue exhibited normal pancreatic morphology, but altered activation of PERK signalling, including increases in Activating Transcription Factor (ATF) 4 accumulation and autophagy. Upon induction of pancreatic injury, STC2Tg mice exhibited limited increases in circulating amylase levels and increased maintenance of cellular junctions. This study links STC2 to the pathological activation of PERK in vivo, and suggests involvement of STC2 in responding to pancreatic acinar cell injury.
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影响因子：
4.8
作者：
Laitusis, AL;Brostrom, MA;Brostrom, CO
通讯作者：
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影响因子：
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DOI：
10.1152/ajpendo.00268.2004
发表时间：
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