Acute respiratory distress syndrome (ARDS) is difficult to treat and has a high mortality rate. Mesenchymal stem cells (MSCs) have an important therapeutic effect in ARDS. While the mechanism of MSC migration to the lungs remains unclear, the role of MSCs is of great clinical significance. To this end, we constructed vimentin knockout mice, extracted bone MSCs from the mice, and used them for the treatment of LPS-induced ARDS. H&E staining and Masson staining of mouse lung tissue allowed us to assess the degree of damage and fibrosis of mouse lung tissue. By measuring serum TNF-α, TGF-β, and INF-γ, we were able to monitor the release of inflammatory factors. Finally, through immunoprecipitation and gene knockout experiments, we identified upstream molecules that regulate vimentin and elucidated the mechanism that mediates MSC migration. As a result, we found that MSCs from wild-type mice can significantly alleviate ARDS and reduce lung inflammation, while vimentin gene knockout reduced the therapeutic effect of MSCs in ARDS. Cytological experiments showed that vimentin gene knockout can significantly inhibit the migration of MSCs and showed that it changes the proliferation and differentiation status of MSCs. Further experiments found that vimentin’s regulation of MSC migration is mainly mediated by Rab7a. Rab7a knockout blocked the migration of MSCs and weakened the therapeutic effect of MSCs in ARDS. In conclusion, we have shown that the Vimentin-Rab7a pathway mediates migration of MSCs and leads to therapeutic effects in ARDS.

中文翻译：

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Vimentin-Rab7a 通路介导 MSC 的迁移并导致对 ARDS 的治疗作用

急性呼吸窘迫综合征（ARDS）治疗难度大，死亡率高。间充质干细胞 (MSCs) 在 ARDS 中具有重要的治疗作用。虽然 MSC 迁移到肺部的机制尚不清楚，但 MSC 的作用具有重要的临床意义。为此，我们构建了波形蛋白敲除小鼠，从小鼠中提取了骨间充质干细胞，并将其用于治疗 LPS 诱导的 ARDS。小鼠肺组织的 H&E 染色和 Masson 染色使我们能够评估小鼠肺组织的损伤和纤维化程度。通过测量血清 TNF - α、TGF- β和 INF- γ，我们能够监测炎症因子的释放。最后，通过免疫沉淀和基因敲除实验，我们确定了调节波形蛋白的上游分子并阐明了介导 MSC 迁移的机制。结果，我们发现来自野生型小鼠的MSCs可以显着缓解ARDS并减轻肺部炎症，而vimentin基因敲除降低了MSCs对ARDS的治疗效果。细胞学实验表明，vimentin基因敲除可显着抑制MSCs的迁移，表明其改变了MSCs的增殖分化状态。进一步的实验发现波形蛋白对MSC迁移的调节主要由Rab7a介导。Rab7a 敲除阻断了 MSCs 的迁移并削弱了 MSCs 对 ARDS 的治疗作用。综上所述，