A murine model of acute lung injury identifies growth factors to promote tissue repair and their biomarkers
A murine model of acute lung injury identifies growth factors to promote tissue repair and their biomarkers
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急性肺损伤的小鼠模型确定了促进组织修复的生长因子及其生物标志物
DOI：
10.1111/gtc.12659
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发表时间：
2018
期刊：
影响因子：
2.1
通讯作者：
Nakano Hiroyasu
中科院分区：
文献类型：
--
作者：
Kurosawa Takeyuki;Miyoshi Shion;Yamazaki Soh;Nishina Takashi;Mikami Tetuo;Oikawa Akira;Homma Sakae;Nakano Hiroyasu
Ⅱ型肺泡上皮细胞（AEC 2）在急性肺损伤后Ⅰ型AECs的再生中起着至关重要的作用。AEC 2再生的机制尚未完全了解。为了解决这个问题，我们在此研究了一种小鼠急性肺损伤模型，该模型使用在溶菌酶M启动子（LysM-DTR）控制下表达人白喉毒素受体（DTR）的小鼠。DT注射诱导LysM-DTR小鼠中AEC 2、肺泡巨噬细胞和骨髓（BM）源性髓样细胞耗竭，并且小鼠在DT注射后6天内死亡。DT注射后24小时出现凋亡的AEC 2和细支气管上皮细胞，而在72-96小时，Ki 67阳性增殖细胞出现在LysM-DTR小鼠肺的肺泡和细支气管中。将野生型BM细胞转移到LysM-DTR小鼠中加速了AEC 2的再生，沿着几种生长因子的上调。此外，与WT小鼠相比，DT注射后LysM-DTR小鼠血清中的几种代谢物显著降低，表明这些代谢物可能是预测AEC 2s损伤的生物标志物。总之，LysM-DTR小鼠可能有助于识别促进肺修复的生长因子和预测肺损伤严重程度的代谢物。
Type II alveolar epithelial cells (AEC2s) play a crucial role in the regeneration of type I AECs after acute lung injury. The mechanisms underlying the regeneration of AEC2s are not fully understood. To address this issue, here, we investigated a murine model of acute lung injury using mice expressing humanDiphtheria Toxin Receptor (DTR)under the control ofLysozyme Mpromoter (LysM‐DTR). DT injection induced the depletion of AEC2s, alveolar macrophages, and bone marrow (BM)‐derived myeloid cells inLysM‐DTRmice, and the mice died within 6 days after DT injection. Apoptotic AEC2s and bronchiolar epithelial cells appeared at 24 hr, whereas Ki67‐positive proliferating cells appeared in the alveoli and bronchioles in the lung ofLysM‐DTRmice at 72–96 hr after DT injection. Transfer of wild‐type BM cells intoLysM‐DTRmice accelerated the regeneration of AEC2s along with the up‐regulation of several growth factors. Moreover, several metabolites were significantly decreased in the sera ofLysM‐DTRmice compared with WT mice after DT injection, suggesting that these metabolites might be biomarkers to predict AEC2s injury. Together,LysM‐DTRmice might be useful to identify growth factors to promote lung repair and the metabolites to predict the severity of lung injury.