Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti‐inflammatory and potent inflammation pro‐resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)‐induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor‐β₁ (TGF‐β₁) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.

中文翻译：

---

Protectin DX 部分通过 ALX/PI3K 信号通路促进上皮损伤修复和抑制纤维增殖

急性呼吸窘迫综合征/急性肺损伤 (ARDS/ALI) 在组织学上以广泛的肺泡屏障破坏和过度的纤维增殖反应为特征。Protectin DX (PDX) 显示出抗炎和有效的炎症促进作用。我们试图研究 PDX 是否通过调节上皮细胞损伤修复、细胞凋亡和成纤维细胞活化来减轻 LPS（脂多糖）诱导的肺损伤。在体内，气管内注射 LPS 后以 200 ng/只小鼠腹腔注射 PDX，显着刺激 II 型肺泡上皮细胞（AT II 细胞）的增殖，减少 AT II 细胞的凋亡，从而减轻肺损伤由 LPS 诱导。此外，分离和培养原代 II 型肺泡细胞以评估 PDX 对伤口修复的影响，体外细胞凋亡、增殖和转分化。我们还研究了 PDX 对原代大鼠肺成纤维细胞增殖和肌成纤维细胞分化的影响。我们的研究结果表明，PDX 通过诱导 AT II 细胞增殖和减少 LPS 诱导的 AT II 细胞凋亡来促进原代 AT II 细胞伤口闭合，并促进 AT II 细胞转分化。此外，PDX 抑制转化生长因子-β₁ (TGF-β1 ₎诱导纤维增殖、成纤维细胞胶原蛋白产生和肌成纤维细胞转化。此外，PDX 对上皮伤口愈合和增殖、成纤维细胞增殖和活化的影响部分通过 ALX/PI3K 信号通路。目前的这些数据确定了一种针对气道上皮细胞和纤维增殖的新的 PDX 机制，这些机制有可能用于治疗 ARDS/ALI。