Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang 325027, China.
Birmingham Acute Care Research Group, Institute of Inflammation and Aging, University of Birmingham, Birmingham B15 2TT, UK.
Biochem Pharmacol. 2020 Jul;177:113955. doi: 10.1016/j.bcp.2020.113955. Epub 2020 Apr 3.
Vitamin D regulates cell proliferation, inhibits cytokines release at sites of inflammation and reduces inflammatory responses. In this study, the aim was to investigate whether exogenous vitamin D attenuates LPS-induced lung injury via modulating epithelial cell proliferation, migration, apoptosis and epithelial mesenchymal transition (EMT). Murine and in vitro primary type II alveolar epithelial cell work were included in this study. In vivo, mice were mildly vitamin D deficient, 0.1, 1.5, 10 mg/kg 1,25(OH)-vitamin D or 25(OH)-vitamin D was administrated by means of an intra-gastric injection for 14 days pre-intra-tracheal (IT) LPS, which remarkedly promoted alveolar epithelial type II cells proliferation, inhibited ATII cells apoptosis and inhibited EMT, with the outcome of attenuated LPS-induced lung injury. In vitro, vitamin D stimulated epithelial cell scratch wound repair, reduced primary ATII cells apoptosis as well. Vitamin D promoted primary human ATII cells proliferation through the PI3K/AKT signaling pathway and activation of vitamin D receptor (VDR). Moreover, vitamin D inhibited EMT in response to TGF-β, which was vitamin D receptor dependent. In conclusion, vitamin D attenuates lung injury via stimulating ATII cells proliferation and migration, reducing epithelial cell apoptosis and inhibits TGF-β induced EMT. Together, these results suggest that vitamin D has therapeutic potential for the resolution of ARDS.
维生素 D 可调节细胞增殖，抑制炎症部位细胞因子的释放，并减轻炎症反应。本研究旨在探讨外源性维生素 D 是否通过调节上皮细胞增殖、迁移、凋亡和上皮-间充质转化（EMT）来减轻 LPS 诱导的肺损伤。本研究包括了动物和体外原代 II 型肺泡上皮细胞的研究。在体内，通过胃内注射 0.1、1.5、10mg/kg 1,25(OH)-维生素 D 或 25(OH)-维生素 D，使小鼠处于轻度维生素 D 缺乏状态 14 天，然后进行气管内 LPS 注射，这显著促进了肺泡上皮 II 型细胞的增殖，抑制了 ATII 细胞的凋亡并抑制了 EMT，从而减轻了 LPS 诱导的肺损伤。在体外，维生素 D 刺激上皮细胞划痕修复，并减少原代 ATII 细胞的凋亡。维生素 D 通过 PI3K/AKT 信号通路和维生素 D 受体（VDR）的激活促进原代人 ATII 细胞的增殖。此外，维生素 D 抑制了 TGF-β诱导的 EMT，这是维生素 D 受体依赖性的。总之，维生素 D 通过刺激 ATII 细胞增殖和迁移、减少上皮细胞凋亡以及抑制 TGF-β诱导的 EMT 来减轻肺损伤。综上所述，维生素 D 具有治疗 ARDS 的潜力。
