Lipopolysaccharide alters VEGF-A secretion of mesenchymal stem cells via the integrin β3-PI3K-AKT pathway

Background Mesenchymal stem cells (MSCs) represent one of the most promising adult stem cells. Different in vivo inflammatory microenvironments impact the capacity of MSCs. Promoting angiogenesis is one mechanism by which MSCs mediate pulmonary protection. Objective Our study aims to evaluate the ef...

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Veröffentlicht in:Molecular & cellular toxicology 2024, Vol.20 (1), p.59-66
Hauptverfasser: Mei, Shuya, Qin, Shaojie, Tang, Ri, Xu, Qiaoyi, Hu, Yue, Feng, Jinhua, He, Zhengyu, Gao, Yuan, Li, Hui, Xing, Shunpeng
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Sprache:eng
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Zusammenfassung:Background Mesenchymal stem cells (MSCs) represent one of the most promising adult stem cells. Different in vivo inflammatory microenvironments impact the capacity of MSCs. Promoting angiogenesis is one mechanism by which MSCs mediate pulmonary protection. Objective Our study aims to evaluate the effects of lipopolysaccharide (LPS) on the proangiogenic capacity of MSCs. Results Human adipose-derived MSCs (hADSCs) were treated with 1 μg/ml LPS to simulate the septic microenvironment. In addition, cilengitide, an integrin β3 inhibitor, and GSK690693, an AKT inhibitor, were used to inhibit integrin β3 and AKT prior to LPS treatment to clarify the role of integrin β3 and AKT. Finally, cells and conditioned media were collected for analysis at 2, 4, and 8 h after LPS stimulation. Vascular endothelial growth factor A (VEGF-A) in human adipose-derived MSCs-conditioned media (hADSCs-CM) was measured by ELISA. The expression of the integrin β3-PI3K-AKT pathway in hADSCs was assessed by western blotting and immunostaining. The proangiogenic effects of hADSCs-CM on human umbilical vein-derived endothelial cells (HUVECs) were assessed by tubule formation assay. LPS treatment increased VEGF-A secretion of hADSCs at 2 h, followed by a decrease at 4 and 8 h; the integrin β3-PI3K-AKT pathway in hADSCs was activated 8 h after LPS challenge; integrin β3 and AKT inhibition reduced PI3K-AKT activation and improved hADSCs-secreted VEGF-A and HUVECs tubule formation. Conclusion In conclusion, VEGF-A secretion of MSCs has been prolongedly inhibited via the integrin β3-PI3K-AKT pathway in the LPS challenge.
ISSN:1738-642X
2092-8467
DOI:10.1007/s13273-022-00315-0