Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway

Abstract Background Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has b...

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Main Authors: Manliang Guo, Shiqi Li, Chuan Li, Xueyan Mao, Liru Tian, Xintong Yang, Caixia Xu, Mian Zeng
Format: Article
Language:English
Published: BMC 2024-03-01
Series:BMC Infectious Diseases
Subjects:
Online Access:https://doi.org/10.1186/s12879-024-09204-4
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author Manliang Guo
Shiqi Li
Chuan Li
Xueyan Mao
Liru Tian
Xintong Yang
Caixia Xu
Mian Zeng
author_facet Manliang Guo
Shiqi Li
Chuan Li
Xueyan Mao
Liru Tian
Xintong Yang
Caixia Xu
Mian Zeng
author_sort Manliang Guo
collection DOAJ
description Abstract Background Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury. Methods To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis. Results Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSCWnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway. Conclusions Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.
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spelling doaj.art-702652fdad4c4997a3bd9e4f701723d82024-03-24T12:11:32ZengBMCBMC Infectious Diseases1471-23342024-03-0124111310.1186/s12879-024-09204-4Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathwayManliang Guo0Shiqi Li1Chuan Li2Xueyan Mao3Liru Tian4Xintong Yang5Caixia Xu6Mian Zeng7Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen UniversityResearch Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen UniversityResearch Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen UniversityResearch Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen UniversityAbstract Background Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury. Methods To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis. Results Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSCWnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway. Conclusions Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.https://doi.org/10.1186/s12879-024-09204-4Wnt5aMesenchymal stem cellsEndothelial cell injuryAcute lung injuryPI3K/AKT signaling
spellingShingle Manliang Guo
Shiqi Li
Chuan Li
Xueyan Mao
Liru Tian
Xintong Yang
Caixia Xu
Mian Zeng
Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway
BMC Infectious Diseases
Wnt5a
Mesenchymal stem cells
Endothelial cell injury
Acute lung injury
PI3K/AKT signaling
title Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway
title_full Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway
title_fullStr Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway
title_full_unstemmed Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway
title_short Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway
title_sort overexpression of wnt5a promoted the protective effect of mesenchymal stem cells on lipopolysaccharide induced endothelial cell injury via activating pi3k akt signaling pathway
topic Wnt5a
Mesenchymal stem cells
Endothelial cell injury
Acute lung injury
PI3K/AKT signaling
url https://doi.org/10.1186/s12879-024-09204-4
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