TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells.
TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells.
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DOI：
10.1016/j.immuni.2018.04.021
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发表时间：
2018-07-17
期刊：
影响因子：
32.4
通讯作者：
Hu H
中科院分区：
文献类型：
--
作者：
Luo J;Qian A;Oetjen LK;Yu W;Yang P;Feng J;Xie Z;Liu S;Yin S;Dryn D;Cheng J;Riehl TE;Zholos AV;Stenson WF;Kim BS;Hu H
肠道巨噬细胞对胃肠道（GI）的稳态至关重要，但我们对它们在调节肠道运动中的作用的理解是不完整的。在这里，我们报告说，CX 3C趋化因子受体1表达肌层巨噬细胞（巨噬细胞）需要维持正常的胃肠道运动。Escherichia coli表达瞬时受体电位香草酸4（TRPV 4）通道，其感知热、机械和化学线索。选择性药理学抑制TRPV 4或从巨噬细胞中条件性删除TRPV 4可降低肠蠕动，并足以逆转与化疗相关的GI运动亢进。从机制上讲，通过TRPV 4刺激结肠促进前列腺素E2的释放，并通过肠平滑肌细胞中的前列腺素E受体信号传导以旁分泌方式引起结肠收缩，而无需肠神经系统的输入。总的来说，我们的数据确定TRPV 4-表达的TRPV 4是维持正常GI运动所需的重要组成部分，并为GI运动障碍提供了潜在的药物靶点。肠道巨噬细胞如何调节肠道运动仍然知之甚少。Luo等人证明，表达TRPV 4通道的肌层巨噬细胞通过直接影响肠平滑肌细胞的功能（不依赖于肠神经系统）来促进GI运动。
Intestinal macrophages are critical for gastrointestinal (GI) homeostasis, but our understanding of their role in regulating intestinal motility is incomplete. Here, we report that CX3C chemokine receptor 1-expressing muscularis macrophages (MMs) were required to maintain normal GI motility. MMs expressed the transient receptor potential vanilloid 4 (TRPV4) channel, which senses thermal, mechanical, and chemical cues. Selective pharmacologic inhibition of TRPV4 or conditional deletion of TRPV4 from macrophages decreased intestinal motility and was sufficient to reverse the GI hypermotility that is associated with chemotherapy treatment. Mechanistically, stimulation of MMs via TRPV4 promoted the release of prostaglandin E2 and elicited colon contraction in a paracrine manner via prostaglandin E receptor signaling in intestinal smooth muscle cells without input from the enteric nervous system. Collectively, our data identify TRPV4-expressing MMs as an essential component required for maintaining normal GI motility and provide potential drug targets for GI motility disorders. How intestinal macrophages regulate intestinal motility remains poorly understood. Luo et al. demonstrate that muscularis macrophages expressing the TRPV4 channel promote GI motility by directly affecting the function of intestinal smooth muscle cells independent of the enteric nervous system.
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DOI：
10.1158/1078-0432.ccr-16-3122
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brown JM;Recht L;Strober S
通讯作者：
Strober S
影响因子：
29.4
作者：
Cenac, Nicolas;Bautzova, Tereza;Vergnolle, Nathalie
通讯作者：
Vergnolle, Nathalie
影响因子：
6.2
作者：
Boesmans, Werend;Lasrado, Reena;Pachnis, Vassilis
通讯作者：
Pachnis, Vassilis
影响因子：
8.7
作者：
Bain CC;Mowat AM
通讯作者：
Mowat AM
影响因子：
4.3
作者：
De Schepper S;Stakenborg N;Matteoli G;Verheijden S;Boeckxstaens GE
通讯作者：
Boeckxstaens GE