Oxytocin evokes a pulsatile PGE2 release from ileum mucosa and is required for repair of intestinal epithelium after injury.
Oxytocin evokes a pulsatile PGE2 release from ileum mucosa and is required for repair of intestinal epithelium after injury.
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DOI：
10.1038/srep11731
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发表时间：
2015-07-10
影响因子：
4.6
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Chen D;Zhao J;Wang H;An N;Zhou Y;Fan J;Luo J;Su W;Liu C;Li J
我们测量了大鼠回肠粘膜的短路电流（Isc），以确定催产素（OT）对小肠粘膜分泌的影响。我们在大鼠回肠粘膜中发现了由 OT 触发的 COX-2 衍生的脉动 PGE2 释放。 OT 受体 (OTR) 在肠隐窝上皮细胞中表达。值得注意的是，OT 引起回肠隐窝中 [Ca2+]i 的动态变化，这是 PGE2 脉冲式释放的原因。 OT 改善了 5-FU、辐射或 DSS 诱导的体内损伤，包括改善体重减轻、降低绒毛高度以及隐窝转运放大细胞和隐窝存活受损。此外，OT 对肠道损伤的这些保护作用可以通过联合使用 PGE2 选择性抑制剂 AH6809 来消除。我们的研究结果强烈表明，OT 作为一种新型且重要的肠粘膜屏障调节剂，是损伤后肠上皮修复所必需的。考虑到 OT 是 FDA 批准的药物，这项工作揭示了一种潜在的新颖且安全的方法来对抗或预防放化疗引起的肠道损伤或治疗 IBD。
We measured the short-circuit current (Isc) in rat ileum mucosa to identify the effect of oxytocin (OT) on mucosal secretion in small intestine. We identified a COX-2-derived pulsatile PGE2 release triggered by OT in rat ileum mucosa. OT receptors (OTR) are expressed in intestine crypt epithelial cells. Notably, OT evoked a dynamic change of [Ca2+]i in ileum crypts, which was responsible for this pulsatile release of PGE2. OT ameliorated 5-FU-, radiation- or DSS- induced injury in vivo, including the improvement of weight loss, reduced villus height and impaired survival of crypt transit-amplifying cells as well as crypt. Moreover, these protective effects of OT against intestinal injury were eliminated by coadministration of a selective inhibitor of PGE2, AH6809. Our findings strongly suggest that OT, a novel and important regulator of intestine mucosa barrier, is required for repair of intestinal epithelium after injury. Considering that OT is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent chemo-radiotherapy induced intestine injury or to treat IBD.
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影响因子：
3.7
作者：
Olsen Hult LT;Kleiveland CR;Fosnes K;Jacobsen M;Lea T
通讯作者：
Lea T
影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
影响因子：
64.8
作者：
Kosfeld, M;Heinrichs, M;Fehr, E
通讯作者：
Fehr, E
DOI：
10.1152/ajpgi.1997.272.3.g681
发表时间：
1997-03-01
影响因子：
4.5
作者：
Morimoto, K;Sugimoto, Y;Ichikawa, A
通讯作者：
Ichikawa, A
影响因子：
3.4
作者：
HANSON, WR;THOMAS, C
通讯作者：
THOMAS, C