Abstract：
BACKGROUND: The major complication of Obliterative Bronchiolitis (OB) is characterized by epithelial cell loss, fibrosis, and luminal occlusion of the terminal small airways, which limits the long-term survival of the recipient after lung transplantation. However, the underlying mechanisms are still not fully clarified. This research aims to investigate whether iron overload-induced ferroptosis is involved in OB development and provide a new target for OB prevention.
METHODS: Allograft orthotopic tracheal transplantation in mice was applied in our study. Ferrostatin-1 and deferoxamine were administrated to inhibit ferroptosis and get rid of ferric iron, while iron dextran was used to induce an iron overload condition in the recipient. The histological examination, luminal occlusion rate, collagen deposition, iron level, ferroptosis marker (GPX4, PTGS2), and mitochondrial morphological changes of the graft were evaluated in mice.
RESULTS: Our research indicated that ferroptosis and iron overload contribute to OB development, while ferroptosis inhibition and iron chelator could reverse the changes. Iron overload exacerbated OB development after orthotopic tracheal transplantation via promoting ferroptosis.
CONCLUSIONS: Overall, this research demonstrated that iron overload-induced ferroptosis is involved in OB, which may be a potential therapeutic target for OB after lung transplantation.
METHODS: Allograft orthotopic tracheal transplantation in mice was applied in our study. Ferrostatin-1 and deferoxamine were administrated to inhibit ferroptosis and get rid of ferric iron, while iron dextran was used to induce an iron overload condition in the recipient. The histological examination, luminal occlusion rate, collagen deposition, iron level, ferroptosis marker (GPX4, PTGS2), and mitochondrial morphological changes of the graft were evaluated in mice.
RESULTS: Our research indicated that ferroptosis and iron overload contribute to OB development, while ferroptosis inhibition and iron chelator could reverse the changes. Iron overload exacerbated OB development after orthotopic tracheal transplantation via promoting ferroptosis.
CONCLUSIONS: Overall, this research demonstrated that iron overload-induced ferroptosis is involved in OB, which may be a potential therapeutic target for OB after lung transplantation.
摘要：
背景：闭塞性细支气管炎（OB）的主要并发症是上皮细胞丢失，纤维化，和末端小气道的管腔闭塞，这限制了肺移植后受体的长期存活。然而,基本机制仍未完全阐明。本研究旨在探讨铁过载诱导的铁凋亡是否参与OB的发生，为OB的预防提供新的靶点。
方法：本研究采用小鼠原位气管移植。给予Ferrostatin-1和去铁胺抑制铁凋亡，去除三价铁，而右旋糖酐铁被用来诱导受体的铁过载条件。组织学检查,管腔闭塞率,胶原蛋白沉积，铁水平,铁凋亡标记（GPX4，PTGS2），并在小鼠中评估了移植物的线粒体形态变化。
结果：我们的研究表明，铁沉积和铁过载有助于OB的发展，而铁凋亡抑制和铁螯合剂可以逆转这种变化。铁过载通过促进铁凋亡加剧了原位气管移植后OB的发育。
结论：总体而言，这项研究表明铁过载诱导的铁凋亡与OB有关，这可能是肺移植后OB的潜在治疗靶点。
方法：本研究采用小鼠原位气管移植。给予Ferrostatin-1和去铁胺抑制铁凋亡，去除三价铁，而右旋糖酐铁被用来诱导受体的铁过载条件。组织学检查,管腔闭塞率,胶原蛋白沉积，铁水平,铁凋亡标记（GPX4，PTGS2），并在小鼠中评估了移植物的线粒体形态变化。
结果：我们的研究表明，铁沉积和铁过载有助于OB的发展，而铁凋亡抑制和铁螯合剂可以逆转这种变化。铁过载通过促进铁凋亡加剧了原位气管移植后OB的发育。
结论：总体而言，这项研究表明铁过载诱导的铁凋亡与OB有关，这可能是肺移植后OB的潜在治疗靶点。
