Abstract
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.
Highlights
Acute respiratory distress syndrome (ARDS) refers to diffuse lung injury caused by severe infection, trauma, shock, or surgery
We found for the first time that vimentin mediated the migration and colonization of Mesenchymal stem cells (MSCs) in damaged lung tissues, thereby playing a role in the treatment of ARDS, and elucidated the mechanism showing that vimentin is regulated by Rab7a to effect the migration of MSCs
The results show that MSCs can effectively reduce LPS-induced lung injury, lung congestion, and edema and relieve the exudation of inflammatory cells (Figures 2(a) and 2(b))
Summary
Acute respiratory distress syndrome (ARDS) refers to diffuse lung injury caused by severe infection, trauma, shock, or surgery. Its main pathophysiological changes are damage to alveolar capillary endothelial cells and alveolar epithelial cells, which leads to increased alveolar membrane permeability, causing a large amount of protein-rich fluid to leak out of the lung interstitium and alveoli Repairing these damaged cells is the key to the early treatment of ARDS. We speculated that Vimentin-Rab7a plays an important role in mediating the migration of MSCs to the damaged lung tissue and the treatment of ARDS, and this aspect of work has not yet been reported. We found for the first time that vimentin mediated the migration and colonization of MSCs in damaged lung tissues, thereby playing a role in the treatment of ARDS, and elucidated the mechanism showing that vimentin is regulated by Rab7a to effect the migration of MSCs
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