New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1
Abstract Background Microvesicles (MVs) derived from human bone marrow mesenchymal stem cell (MSC) were demonstrated to restore lung protein permeability and attenuate acute lung injury. In our previous study, we found that MSC MV increased sphingosine-1-phosphate (S1P) kinase1 mRNA levels in injure...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-10-01
|
| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-03177-4 |
| _version_ | 1811226809187958784 |
|---|---|
| author | Lifang Ye Jieqiong Song Yijun Zheng Ming Zhong Jun Liu Duming Zhu Shuling Hu |
| author_facet | Lifang Ye Jieqiong Song Yijun Zheng Ming Zhong Jun Liu Duming Zhu Shuling Hu |
| author_sort | Lifang Ye |
| collection | DOAJ |
| description | Abstract Background Microvesicles (MVs) derived from human bone marrow mesenchymal stem cell (MSC) were demonstrated to restore lung protein permeability and attenuate acute lung injury. In our previous study, we found that MSC MV increased sphingosine-1-phosphate (S1P) kinase1 mRNA levels in injured human lung microvascular endothelial cells (HLMVEC) significantly. However, the role of S1P signaling in MSC MV to restore lung protein permeability is unknown. Methods In this study, we hypothesized that MSC MV might restore lung permeability in part through increasing intracellular S1P signaling pathway in injured HLMVEC independent of S1P receptors. We used the transwell co-culture system to study the effect of MSC MV on protein permeability of Lipopolysaccharide (LPS) damaged HLMVEC. Results Our results showed that LPS significantly increased the permeability of HLMVEC to FITC-dextran (70 kDa) within 24 h. MSC MV restores this permeability and, to a large extent, prevents the cytoskeleton protein F-actin from recombining into “actin stress fibers,” and restores the positions of tight junctions and adhesion junctions in the damaged HLMVEC. This therapeutic effect of MSC MV was related to the increase in the S1P level in injured HLMVEC and was not eliminated when adding the antagonist of S1P receptor, suggesting that MSC MV to restore lung permeability was independent of S1P receptors on HLMVEC. Laser confocal further observed that Ca2+ mobilization and Rac1 activation in LPS injured HLMVEC were increased in parallel with the increase in intracellular S1P level after MSC MV treatment. Conclusions In short, MSC MV partially restored protein permeability across HLMVEC through the intracellular S1P signaling pathway independent of S1P receptor-1. |
| first_indexed | 2024-04-12T09:31:23Z |
| format | Article |
| id | doaj.art-7a99c5bad3b04938a5d88a10b82966ed |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-12T09:31:23Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-7a99c5bad3b04938a5d88a10b82966ed2022-12-22T03:38:21ZengBMCStem Cell Research & Therapy1757-65122022-10-0113111110.1186/s13287-022-03177-4New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1Lifang Ye0Jieqiong Song1Yijun Zheng2Ming Zhong3Jun Liu4Duming Zhu5Shuling Hu6Department of Intensive Care Medicine, Medical School, Zhongshan Hospital, Fudan UniversityDepartment of Intensive Care Medicine, Medical School, Zhongshan Hospital, Fudan UniversityDepartment of Intensive Care Medicine, Medical School, Zhongshan Hospital, Fudan UniversityDepartment of Intensive Care Medicine, Medical School, Zhongshan Hospital, Fudan UniversityDepartment of Intensive Care Medicine, Gusu School, Suzhou Hospital, Nanjing Medical UniversityDepartment of Intensive Care Medicine, Medical School, Zhongshan Hospital, Fudan UniversityDepartment of Intensive Care Medicine, Medical School, Zhongshan Hospital, Fudan UniversityAbstract Background Microvesicles (MVs) derived from human bone marrow mesenchymal stem cell (MSC) were demonstrated to restore lung protein permeability and attenuate acute lung injury. In our previous study, we found that MSC MV increased sphingosine-1-phosphate (S1P) kinase1 mRNA levels in injured human lung microvascular endothelial cells (HLMVEC) significantly. However, the role of S1P signaling in MSC MV to restore lung protein permeability is unknown. Methods In this study, we hypothesized that MSC MV might restore lung permeability in part through increasing intracellular S1P signaling pathway in injured HLMVEC independent of S1P receptors. We used the transwell co-culture system to study the effect of MSC MV on protein permeability of Lipopolysaccharide (LPS) damaged HLMVEC. Results Our results showed that LPS significantly increased the permeability of HLMVEC to FITC-dextran (70 kDa) within 24 h. MSC MV restores this permeability and, to a large extent, prevents the cytoskeleton protein F-actin from recombining into “actin stress fibers,” and restores the positions of tight junctions and adhesion junctions in the damaged HLMVEC. This therapeutic effect of MSC MV was related to the increase in the S1P level in injured HLMVEC and was not eliminated when adding the antagonist of S1P receptor, suggesting that MSC MV to restore lung permeability was independent of S1P receptors on HLMVEC. Laser confocal further observed that Ca2+ mobilization and Rac1 activation in LPS injured HLMVEC were increased in parallel with the increase in intracellular S1P level after MSC MV treatment. Conclusions In short, MSC MV partially restored protein permeability across HLMVEC through the intracellular S1P signaling pathway independent of S1P receptor-1.https://doi.org/10.1186/s13287-022-03177-4Mesenchymal stem cellMicrovesiclesHuman lung microvascular endothelial cellPulmonary endothelial permeabilitySphingosine-1-phosphate |
| spellingShingle | Lifang Ye Jieqiong Song Yijun Zheng Ming Zhong Jun Liu Duming Zhu Shuling Hu New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1 Stem Cell Research & Therapy Mesenchymal stem cell Microvesicles Human lung microvascular endothelial cell Pulmonary endothelial permeability Sphingosine-1-phosphate |
| title | New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1 |
| title_full | New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1 |
| title_fullStr | New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1 |
| title_full_unstemmed | New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1 |
| title_short | New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1 |
| title_sort | new mechanism for mesenchymal stem cell microvesicle to restore lung permeability intracellular s1p signaling pathway independent of s1p receptor 1 |
| topic | Mesenchymal stem cell Microvesicles Human lung microvascular endothelial cell Pulmonary endothelial permeability Sphingosine-1-phosphate |
| url | https://doi.org/10.1186/s13287-022-03177-4 |
| work_keys_str_mv | AT lifangye newmechanismformesenchymalstemcellmicrovesicletorestorelungpermeabilityintracellulars1psignalingpathwayindependentofs1preceptor1 AT jieqiongsong newmechanismformesenchymalstemcellmicrovesicletorestorelungpermeabilityintracellulars1psignalingpathwayindependentofs1preceptor1 AT yijunzheng newmechanismformesenchymalstemcellmicrovesicletorestorelungpermeabilityintracellulars1psignalingpathwayindependentofs1preceptor1 AT mingzhong newmechanismformesenchymalstemcellmicrovesicletorestorelungpermeabilityintracellulars1psignalingpathwayindependentofs1preceptor1 AT junliu newmechanismformesenchymalstemcellmicrovesicletorestorelungpermeabilityintracellulars1psignalingpathwayindependentofs1preceptor1 AT dumingzhu newmechanismformesenchymalstemcellmicrovesicletorestorelungpermeabilityintracellulars1psignalingpathwayindependentofs1preceptor1 AT shulinghu newmechanismformesenchymalstemcellmicrovesicletorestorelungpermeabilityintracellulars1psignalingpathwayindependentofs1preceptor1 |