Lung epithelial-specific TRIP-1 overexpression maintains epithelial integrity during hyperoxia exposure.
Lung epithelial-specific TRIP-1 overexpression maintains epithelial integrity during hyperoxia exposure.
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DOI：
10.14814/phy2.13585
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发表时间：
2018-03
影响因子：
2.5
通讯作者：
Ekekezie II
中科院分区：
文献类型：
--
作者：
Nyp MF;Mabry SM;Navarro A;Menden H;Perez RE;Sampath V;Ekekezie II
发生高氧性急性肺损伤(HALI)的动物的损伤发生和程度取决于暴露时的年龄，这表明发育调节的途径/因素必须是启动上皮损伤和随后修复的基础。II型转化生长因子β受体相互作用蛋白-1(TRIP-1)是转化生长因子β信号转导的负性调节因子，是一种发育调节蛋白，对上皮成纤维细胞信号转导具有调节作用。这项研究的目的是评估过度表达TRIP-1的II型肺泡上皮细胞是否受到高氧诱导的上皮损伤的保护，进而保护HALI。将高表达TRIP-1或LacZ的大鼠肺上皮细胞(RLE)暴露于85%氧气中4天。建立了表面活性蛋白C(SPC)驱动的TRIP-1过表达小鼠(TRIP-1AECTg+)，并在4周龄时暴露于高氧(>；95%，持续4天)，以评价TRIP-1过表达对HALI的影响。RLE过表达TRIP-1可拮抗高氧诱导的细胞凋亡。在肺泡II型上皮细胞(TRIP-1AECTg+)高表达TRIP-1的小鼠表现出正常的肺发育，磷酸化AKT水平和E-钙粘附素水平增加，并对HALI产生抵抗，表现为转化生长因子β活化、细胞凋亡、肺泡巨噬细胞内流和KC表达减少。综上所述，这些发现表明TRIP-1介导的分子通路的存在，对上皮/急性肺损伤具有保护作用。
The onset and degree of injury occurring in animals that develop hyperoxic acute lung injury (HALI) is dependent on age at exposure, suggesting that developmentally regulated pathways/factors must underlie initiation of the epithelial injury and subsequent repair. Type II TGFβ receptor interacting protein‐1 (TRIP‐1) is a negative regulator of TGFβ signaling, which we have previously shown is a developmentally regulated protein with modulatory effects on epithelial‐fibroblastic signaling. The aim of this study was to assess if type II alveolar epithelial cells overexpressing TRIP‐1 are protected against hyperoxia‐induced epithelial injury, and in turn HALI. Rat lung epithelial cells (RLE) overexpressing TRIP‐1 or LacZ were exposed to 85% oxygen for 4 days. A surfactant protein C (SPC)‐driven TRIP‐1 overexpression mouse (TRIP‐1AECTg+) was generated and exposed to hyperoxia (>95% for 4 days) at 4 weeks of age to assess the effects TRIP‐1 overexpression has on HALI. RLE overexpressing TRIP‐1 resisted hyperoxia‐induced apoptosis. Mice overexpressing TRIP‐1 in their lung type II alveolar epithelial cells (TRIP‐1AECTg+) showed normal lung development, increased phospho‐AKT level and E‐cadherin, along with resistance to HALI, as evidence by less TGFβ activation, apoptosis, alveolar macrophage influx, KC expression. Taken together, these findings point to existence of a TRIP‐1 mediated molecular pathway affording protection against epithelial/acute lung injury.