TY - JOUR T1 - Kruppel-样因子4是STAT3-Smad2的调节器在ATII细胞肺发育和高氧性肺损伤JF期间确定ATII细胞命运 - 欧洲呼吸杂志JO - 欧洲呼吸j执行 - 10.1183 / 13993003.congress-2019.OA3607 VL - 54 - 63增刊SP - OA3607 AU - 莫尔，茉莉花AU - 科赫，曼努埃尔AU - Danopoulos，Soula酒店AU - 埃伯特，海伦AU - Oikonomou，尼科斯AU - Vohlen，克里斯蒂娜AU - Hirani，Dharmesh AU -人阿拉姆，丹尼斯AU - Schermer，伯恩哈德AU - Dötsch，约尔格AU - 亚历杭德雷城堡，米格尔A. Y1 - 2019年9月28日UR - //www.qdcxjkg.com/content/54/suppl_63/OA3607.abstractN2 - 背景：支气管肺发育不良（BPD）的特征在于受损的alveolarization和再生。Kruppel-样因子4（KLF4），转录因子调节细胞内稳态和多能性，高度在肺发育期间，人和小鼠中表达并链接到肺生长arrest.Aim：研究（1）如果高氧肺损伤减少KLF4在小鼠ATII细胞;（2）如果KLF4的ATII特异性损失耗尽ATII细胞的数目;（3）KLF4的ATII细胞vitro.Methods功能：（1）新生小鼠暴露于85％O 2（HYX）或室内空气（NOX）。（2）KLF4的小区特定缺失小鼠中晚期肺发育期间引起。（3）过度表达（Klf4OE）和Klf4的消融（Klf4del; CRISPR / Cas9）在小鼠肺上皮细胞（MLE-12）结果：（1）双免疫荧光染色过程中晚期的鼠肺发育和上皮确定KLF4在ATII细胞细胞在人胎儿肺。 Reduced ATII markers after HYX were linked to reduced Klf4 expression and lung growth. (2) ATII-specific Klf4 ablation during late lung development reduced ATII cells in mice. (3) In MLE-12, HYX decreased Klf4 expression and cell survival. Klf4OE and Klf4del in MLE-12 induced apoptosis and decreased epithelial cell markers. Klf4OE aggravated HYX-related decreased proliferation, activated Smad2 and blocked Stat3 signaling. Inhibition of Smad2, using an inhibitor, activated Stat3. Klf4del activated Stat3 and inhibited Smad2.Conclusion: We identified a novel Klf4-Smad2-Stat3 axis cell homeostasis that HYX disrupts in ATII cells and in lungs of newborn mice, suggesting Klf4 as potential target regulating lung regeneration.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, OA3607.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -