Piezo1 is a mechanically activated ion channel and mediates pressure induced pancreatitis.
Piezo1 is a mechanically activated ion channel and mediates pressure induced pancreatitis.
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Piezo1是一种机械激活的离子通道，介导压力诱导的胰腺炎。
DOI：
10.1038/s41467-018-04194-9
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发表时间：
2018-04-30
影响因子：
16.6
通讯作者：
Liddle RA
中科院分区：
文献类型：
--
作者：
Romac JM;Shahid RA;Swain SM;Vigna SR;Liddle RA
仅仅触摸胰腺可导致酶原过早激活和胰腺炎，但其机制尚不完全清楚。在这里，我们证明胰腺腺泡细胞表达机械感受器Piezo1，在腺体内施加压力会导致胰腺炎。为了确定这种作用是否通过Piezo1激活，我们通过胰管内滴注Piezo1激动剂Yoda1来诱导胰腺炎。由腺体内压力引起的胰腺炎可由Piezo1拮抗剂预防。在胰腺腺泡细胞中，Yoda1刺激钙内流，诱导钙依赖性胰腺损伤。最后，选择性腺泡细胞特异性的Piezo1基因缺失可以保护小鼠免受压力诱导的胰腺炎。因此，胰腺腺泡细胞中Piezo1的激活是胰腺炎的一种机制，这可能解释了为什么在腹部创伤、胰管梗阻、胰腺造影术或胰腺手术中，腺体受到压力后会发生胰腺炎。当预期操作腺体时，PIEZO1阻滞剂可以预防胰腺炎。手术中对胰腺的操作可由于酶原激活而导致急性胰腺炎。在这里，作者表明，机械感受器Piezo1被压力激活，它的激活导致钙依赖的胰腺损伤，而它的抑制对胰腺炎具有保护作用。
Merely touching the pancreas can lead to premature zymogen activation and pancreatitis but the mechanism is not completely understood. Here we demonstrate that pancreatic acinar cells express the mechanoreceptor Piezo1 and application of pressure within the gland produces pancreatitis. To determine if this effect is through Piezo1 activation, we induce pancreatitis by intrapancreatic duct instillation of the Piezo1 agonist Yoda1. Pancreatitis induced by pressure within the gland is prevented by a Piezo1 antagonist. In pancreatic acinar cells, Yoda1 stimulates calcium influx and induces calcium-dependent pancreatic injury. Finally, selective acinar cell-specific genetic deletion of Piezo1 protects mice against pressure-induced pancreatitis. Thus, activation of Piezo1 in pancreatic acinar cells is a mechanism for pancreatitis and may explain why pancreatitis develops following pressure on the gland as in abdominal trauma, pancreatic duct obstruction, pancreatography, or pancreatic surgery. Piezo1 blockade may prevent pancreatitis when manipulation of the gland is anticipated. Manipulation of the pancreas during surgery can induce acute pancreatitis due to zymogen activation. Here the authors show that the mechanoreceptor Piezo1 is activated by pressure and its activation leads to calcium dependent pancreatic injury whereas its inhibition is protective against pancreatitis.
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DOI：
10.4161/chan.21050
发表时间：
2012-07
期刊：
Channels (Austin, Tex.)
影响因子：
--
作者：
Gottlieb PA;Sachs F
通讯作者：
Sachs F
影响因子：
2.2
作者：
Dolenšek J;Rupnik MS;Stožer A
通讯作者：
Stožer A
影响因子：
7.7
作者：
Guo YR;MacKinnon R
通讯作者：
MacKinnon R
影响因子：
7.7
作者：
Cahalan SM;Lukacs V;Ranade SS;Chien S;Bandell M;Patapoutian A
通讯作者：
Patapoutian A
影响因子：
64.8
作者：
Ge, Jingpeng;Li, Wanqiu;Yang, Maojun
通讯作者：
Yang, Maojun