TY - T1的刺激的EP <子> 3 < /订阅>受体引起肺部水肿TRPC6在肺动脉内皮细胞激活的JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.02635 -2021欧元SP - 2102635 AU -田蒋盟Rudi Samapati AU -卡里莫夫克拉森盟Disi Lei盟Lasti Erfinanda AU -维拉养家糊口盟Szandor西蒙斯AU - 6月阴盟Christoph Arenz AU -亚历山大·迪特里希盟-托马斯Gudermann AU - Dieter亚当AU -迈克尔Schaefer盟Joachim养家糊口盟Veit Flockerzi Stefan Uhlig AU - Rolf新加坡国立大学盟盟-沃尔夫冈·m·Kuebler Y1 - 2022/01/01 UR - //www.qdcxjkg.com/content/early/2022/02/24/13993003.02635 - 2021. -抽象N2 -背景前列腺素E2 (PGE2)肺血管通透性增加PGE2的激活受体3 (EP3)这可以解释不良肺的影响EP1 / EP3受体受体激动剂sulprostone病人。PGE2也会导致肺水肿在回应platelet-activating因子(PAF)参谋长。拥堵增加内皮渗透性通过招募阳离子通道瞬时受体电位规范6 (TRPC6)内皮小窝通过酸性鞘磷脂酶(ASMase)。然而,PGE2和EP3的角色在这个途径是未知的。我们假设EP3受体激活可能会增加肺血管渗透性TRPC6激活,因此,协同ASMase-mediated TRPC6在PAF-induced招聘肺部水肿。方法孤立肺,我们测量增加内皮Ca2 +(ΔCa2 +)或者肺重量(Δweight)和内皮caveolar TRPC6丰富以及磷酸化。结果PAF-inducedΔCa2 +和Δweight减毒EP3-deficient老鼠。Sulprostone复制PAF-inducedΔCa2 +和Δweight被药物/基因抑制TRPC6 ASMase或Src-family激酶(SrcFK)。拥堵,但不是sulprostone TRPC6丰度增加内皮细胞膜穴样内陷。拥堵的免疫沉淀反应显示,sulprostone-induced tyrosine-phosphorylation的TRPC6阻止通过抑制磷脂酶C (PLC)或SrcFK。PLC抑制也封锁sulprostone-inducedΔCa2 +Δweight,也抑制SrcFK或胃肠道信号。结论EP3激活触发器通过Gi-dependent肺水肿激活的PLC和后续SrcFK-dependent TRPC6酪氨酸磷酸化。 In PAF-induced lung edema this TRPC6 activation coincides with ASMase-dependent caveolar recruitment of TRPC6, resulting in rapid endothelial Ca2+ influx and barrier failure.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Tian Jiang has nothing to disclose.Conflict of interest: Rudi Samapati has nothing to disclose.Conflict of interest: Sergej Klassen has nothing to disclose.Conflict of interest: Disi Lei has nothing to disclose.Conflict of interest: Vera Jankowski has nothing to disclose.Conflict of interest: Szandor Simmons has nothing to disclose.Conflict of interest: Jun Yin has nothing to disclose.Conflict of interest: Christoph Arenz has nothing to disclose.Conflict of interest: Alexander Dietrich has nothing to disclose.Conflict of interest: Thomas Gudermann has nothing to disclose.Conflict of interest: Dieter Adam has nothing to disclose.Conflict of interest: Michael Schaefer has nothing to disclose.Conflict of interest: Joachim Jankowski has nothing to disclose.Conflict of interest: Veit Flockerzi has nothing to disclose.Conflict of interest: Rolf Nüsing has nothing to disclose.Conflict of interest: Stefan Uhlig has nothing to disclose.Conflict of interest: Wolfgang M. Kuebler has nothing to disclose. ER -