Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS
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 e...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2021/9992381 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832563725313245184 |
|---|---|
| author | Kai Wang Boxiang Du Yan Zhang Congyou Wu Xiuli Wang Xu Zhang Liwei Wang |
| author_facet | Kai Wang Boxiang Du Yan Zhang Congyou Wu Xiuli Wang Xu Zhang Liwei Wang |
| author_sort | Kai Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ada7f9ba65334b44a711caea51c761ac |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-ada7f9ba65334b44a711caea51c761ac2025-02-03T01:12:53ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/99923819992381Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDSKai Wang0Boxiang Du1Yan Zhang2Congyou Wu3Xiuli Wang4Xu Zhang5Liwei Wang6School of Medicine, Tongji University, Shanghai 200092, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Nantong University, Jiangsu 226000, ChinaDepartment of Anesthesiology, Xuzhou Central Hospital, Jiangsu 221009, ChinaDepartment of Anesthesiology, Xuzhou Central Hospital, Jiangsu 221009, ChinaDepartment of Anesthesiology, Xuzhou Central Hospital, Jiangsu 221009, ChinaDepartment of Anesthesiology, Xuzhou Central Hospital, Jiangsu 221009, ChinaSchool of Medicine, Tongji University, Shanghai 200092, ChinaAcute 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.http://dx.doi.org/10.1155/2021/9992381 |
| spellingShingle | Kai Wang Boxiang Du Yan Zhang Congyou Wu Xiuli Wang Xu Zhang Liwei Wang Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS Stem Cells International |
| title | Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS |
| title_full | Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS |
| title_fullStr | Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS |
| title_full_unstemmed | Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS |
| title_short | Vimentin-Rab7a Pathway Mediates the Migration of MSCs and Lead to Therapeutic Effects on ARDS |
| title_sort | vimentin rab7a pathway mediates the migration of mscs and lead to therapeutic effects on ards |
| url | http://dx.doi.org/10.1155/2021/9992381 |
| work_keys_str_mv | AT kaiwang vimentinrab7apathwaymediatesthemigrationofmscsandleadtotherapeuticeffectsonards AT boxiangdu vimentinrab7apathwaymediatesthemigrationofmscsandleadtotherapeuticeffectsonards AT yanzhang vimentinrab7apathwaymediatesthemigrationofmscsandleadtotherapeuticeffectsonards AT congyouwu vimentinrab7apathwaymediatesthemigrationofmscsandleadtotherapeuticeffectsonards AT xiuliwang vimentinrab7apathwaymediatesthemigrationofmscsandleadtotherapeuticeffectsonards AT xuzhang vimentinrab7apathwaymediatesthemigrationofmscsandleadtotherapeuticeffectsonards AT liweiwang vimentinrab7apathwaymediatesthemigrationofmscsandleadtotherapeuticeffectsonards |