Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Jiangsu 215006, P.R. China.
Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6715-6721. doi: 10.3892/mmr.2017.7469. Epub 2017 Sep 12.
The aim of the present study was to examine the role of Wnt signaling in lipopolysaccharide (LPS)‑induced acute respiratory distress syndrome (ARDS). ARDS was induced by LPS and compared in mice treated with either glycogen synthase kinase‑3β inhibitor (GSKI) or PBS. The protein expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor (TNF)‑α, IL‑17, IL‑18 and IL‑1β in the bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific enzyme‑linked immunosorbent assays. The accumulation of neutrophils and macrophages in the BALF were detected using flow cytometry. The extent of pathological lesions was evaluated using an immunohistochemical assay. The differentiation of mesenchymal stem cells (MSCs) into type II alveolar (ATII) epithelial cells was analyzed using immunofluorescence staining. Treatment with GSKI led to maintained body weights and survival in mice with LPS‑induced ARDS. Treatment with GSKI effectively reduced the levels of total protein, albumin, IgM and keratinocyte growth factor in the BALF. Smith scores showed that GSKI significantly alleviated LPS‑induced lung injury. GSKI also functioned to reduce inflammatory cell accumulation and pro‑inflammatory cytokine secretion. Finally, it was found that GSKI promoted the differentiation of MSCs into ATII epithelial cells in vivo. Taken together, the GSKI‑treated mice exhibited reduced acute lung injury through inhibited intra‑fluid inflammatory cell infiltration and decreased expression of pro‑inflammatory cytokines, and GSKI increased the differentiation of MSCs into ATII epithelial cells.
本研究旨在探讨 Wnt 信号通路在脂多糖（LPS）诱导的急性呼吸窘迫综合征（ARDS）中的作用。通过 LPS 诱导 ARDS，并比较用糖原合酶激酶-3β抑制剂（GSKI）或 PBS 处理的小鼠。采用小鼠细胞因子特异性酶联免疫吸附试验检测支气管肺泡灌洗液（BALF）中白细胞介素（IL）-6、IL-8、肿瘤坏死因子（TNF）-α、IL-17、IL-18 和 IL-1β的蛋白表达水平。采用流式细胞术检测 BALF 中中性粒细胞和巨噬细胞的积累。采用免疫组织化学检测评估病理损伤程度。采用免疫荧光染色分析间充质干细胞（MSCs）向 II 型肺泡（ATII）上皮细胞的分化。GSKI 治疗可维持 LPS 诱导的 ARDS 小鼠的体重和存活率。GSKI 治疗可有效降低 BALF 中总蛋白、白蛋白、IgM 和角质细胞生长因子的水平。Smith 评分显示 GSKI 可显著减轻 LPS 诱导的肺损伤。GSKI 还可减少炎症细胞积累和促炎细胞因子分泌。最后，发现 GSKI 可促进 MSC 在体内向 ATII 上皮细胞分化。综上所述，GSKI 治疗可通过抑制肺内炎症细胞浸润和降低促炎细胞因子表达减轻急性肺损伤，并增加 MSC 向 ATII 上皮细胞的分化。
