Acute respiratory distress syndrome (ARDS) is a deadly illness which presents with severe hypoxemia as well as diffuse alveolar damage. Jumonji domain‑containing 3 (JMJD3), which belongs to the UTX/UTY JmjC‑domain protein subfamily, is involved in infection, development, aging and immune disorders. However, the role of JMJD3 in acute lung injury (ALI) is still unclear. The present study explored the roles and potential mechanisms of JMJD3 in ALI. Alveolar epithelial cell‑specific knockout of JMJD3 mice and A549 alveolar epithelial cells were used to investigate the function of JMJD3 in ALI. Lipopolysaccharide (LPS) was used to establish an in vivo and in vitro ALI model. The expression of JMJD3 in murine lung tissue and alveolar epithelial cells was detected. Pathological injury of lung tissue and alveolar epithelial cells was also investigated following inhibition of JMJD3. The results showed that JMJD3 expression was significantly increased in murine lung tissues and in A549 cells following LPS stimulation. JMJD3‑deficient mice in alveolar epithelial cells exhibited alleviated lung pathological injury and ferroptosis following h stimulation. Mechanistically, it was found that JMJD3 knockout could increase the expression of nuclear factor erythroid‑2‑related factor‑2 (Nrf2) in lung tissues challenged with h. However, Nrf2 overexpression by adenovirus could further enhance the anti‑ferroptotic effect from JMJD3 silence in h‑treated A549 cells. Taken together, the present study revealed that JMJD3 deficiency may relieve LPS‑induced ALI by blocking alveolar epithelial ferroptosis in a Nrf2‑dependent manner, which may serve as a novel therapeutic target against ALI.

中文翻译：

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JMJD3缺乏通过以Nrf2依赖性方式抑制肺泡上皮铁死亡来减轻脂多糖诱导的急性肺损伤。

急性呼吸窘迫综合征 (ARDS) 是一种致命的疾病，表现为严重的低氧血症以及弥漫性肺泡损伤。含有 Jumonji 结构域的 3 (JMJD3) 属于 UTX/UTY JmjC 结构域蛋白亚家族，与感染、发育、衰老和免疫疾病有关。然而，JMJD3 在急性肺损伤 (ALI) 中的作用仍不清楚。本研究探讨了 JMJD3 在 ALI 中的作用和潜在机制。使用 JMJD3 小鼠和 A549 肺泡上皮细胞的肺泡上皮细胞特异性敲除来研究 JMJD3 在 ALI 中的功能。脂多糖 (LPS) 用于建立体内和体外阿里模型。检测JMJD3在小鼠肺组织和肺泡上皮细胞中的表达。在抑制 JMJD3 后，还研究了肺组织和肺泡上皮细胞的病理损伤。结果表明，在 LPS 刺激后，小鼠肺组织和 A549 细胞中 JMJD3 的表达显着增加。肺泡上皮细胞中 JMJD3 缺陷的小鼠在 h 刺激后表现出减轻的肺病理损伤和铁死亡。在机制上，发现 JMJD3 敲除可以增加受到 h. 然而，腺病毒过表达 Nrf2 可以进一步增强 H 处理的 A549 细胞中 JMJD3 沉默的抗铁死亡作用。综合起来，