Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS

Kai Wang; Boxiang Du; Yan Zhang; Congyou Wu; Xiuli Wang; Xu Zhang; Liwei Wang

doi:10.1155/2021/9992381

Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS

Stem Cells Int. 2021 Jul 29:2021:9992381. doi: 10.1155/2021/9992381. eCollection 2021.

Authors

Kai Wang^{1

2}, Boxiang Du³, Yan Zhang², Congyou Wu², Xiuli Wang², Xu Zhang², Liwei Wang^{1

2}

Affiliations

¹ School of Medicine, Tongji University, Shanghai 200092, China.
² Department of Anesthesiology, Xuzhou Central Hospital, Jiangsu 221009, China.
³ Department of Anesthesiology, The Second Affiliated Hospital of Nantong University, Jiangsu 226000, China.

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.