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 |
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| creator | Mei, Shuya Qin, Shaojie Tang, Ri Xu, Qiaoyi Hu, Yue Feng, Jinhua He, Zhengyu Gao, Yuan Li, Hui Xing, Shunpeng |
| description | 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. |
| doi_str_mv | 10.1007/s13273-022-00315-0 |
| format | Article |
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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.</description><identifier>ISSN: 1738-642X</identifier><identifier>EISSN: 2092-8467</identifier><identifier>DOI: 10.1007/s13273-022-00315-0</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Angiogenesis ; Biomedical and Life Sciences ; Cell Biology ; Endothelial cells ; Enzyme-linked immunosorbent assay ; Inflammation ; Life Sciences ; Lipopolysaccharides ; Mesenchymal stem cells ; Original Article ; Pharmacology/Toxicology ; Stem cells ; Umbilical vein ; Vascular endothelial growth factor ; Western blotting</subject><ispartof>Molecular & cellular toxicology, 2024, Vol.20 (1), p.59-66</ispartof><rights>The Author(s) under exclusive licence to The Korean Society of Toxicogenomics and Toxicoproteomics 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c319t-676b3d887d7e2e5dece5bab6d6223aa09fc03b6d35d2b5862247bdb28c8f7a683</citedby><cites>FETCH-LOGICAL-c319t-676b3d887d7e2e5dece5bab6d6223aa09fc03b6d35d2b5862247bdb28c8f7a683</cites><orcidid>0000-0003-4500-9888 ; 0000-0002-2796-0832</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13273-022-00315-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13273-022-00315-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Mei, Shuya</creatorcontrib><creatorcontrib>Qin, Shaojie</creatorcontrib><creatorcontrib>Tang, Ri</creatorcontrib><creatorcontrib>Xu, Qiaoyi</creatorcontrib><creatorcontrib>Hu, Yue</creatorcontrib><creatorcontrib>Feng, Jinhua</creatorcontrib><creatorcontrib>He, Zhengyu</creatorcontrib><creatorcontrib>Gao, Yuan</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><creatorcontrib>Xing, Shunpeng</creatorcontrib><title>Lipopolysaccharide alters VEGF-A secretion of mesenchymal stem cells via the integrin β3-PI3K-AKT pathway</title><title>Molecular & cellular toxicology</title><addtitle>Mol. Cell. Toxicol</addtitle><description>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.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Angiogenesis</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Endothelial cells</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Inflammation</subject><subject>Life Sciences</subject><subject>Lipopolysaccharides</subject><subject>Mesenchymal stem cells</subject><subject>Original Article</subject><subject>Pharmacology/Toxicology</subject><subject>Stem cells</subject><subject>Umbilical vein</subject><subject>Vascular endothelial growth factor</subject><subject>Western blotting</subject><issn>1738-642X</issn><issn>2092-8467</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kE1OwzAQRi0EEqVwAVaWWBscO7GTZVW1pWolWBTEznKcSZMqf9guKNfiIJyJQJDYsRrN6HvfSA-h64DeBpTKOxdwJjmhjBFKeRAReoImjCaMxKGQp2gSSB4TEbKXc3Th3IFSEYYimaDDtuzarq16p40ptC0zwLryYB1-XqyWZIYdGAu-bBvc5rgGB40p-lpX2HmosYGqcvit1NgXgMvGw96WDf784ORxzTdkttnhTvviXfeX6CzXlYOr3zlFT8vFbn5Ptg-r9Xy2JYYHiSdCipRncSwzCQyiDAxEqU5FJhjjWtMkN5QPK48ylkbxcA1lmqUsNnEutYj5FN2MvZ1tX4_gvDq0R9sMLxVL2KCIhywcUmxMGds6ZyFXnS1rbXsVUPXtVI1O1QCoH6eKDhAfITeEmz3Yv-p_qC89EnqF</recordid><startdate>2024</startdate><enddate>2024</enddate><creator>Mei, Shuya</creator><creator>Qin, Shaojie</creator><creator>Tang, Ri</creator><creator>Xu, Qiaoyi</creator><creator>Hu, Yue</creator><creator>Feng, Jinhua</creator><creator>He, Zhengyu</creator><creator>Gao, Yuan</creator><creator>Li, Hui</creator><creator>Xing, Shunpeng</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-4500-9888</orcidid><orcidid>https://orcid.org/0000-0002-2796-0832</orcidid></search><sort><creationdate>2024</creationdate><title>Lipopolysaccharide alters VEGF-A secretion of mesenchymal stem cells via the integrin β3-PI3K-AKT pathway</title><author>Mei, Shuya ; Qin, Shaojie ; Tang, Ri ; Xu, Qiaoyi ; Hu, Yue ; Feng, Jinhua ; He, Zhengyu ; Gao, Yuan ; Li, Hui ; Xing, Shunpeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c319t-676b3d887d7e2e5dece5bab6d6223aa09fc03b6d35d2b5862247bdb28c8f7a683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Angiogenesis</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Endothelial cells</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Inflammation</topic><topic>Life Sciences</topic><topic>Lipopolysaccharides</topic><topic>Mesenchymal stem cells</topic><topic>Original Article</topic><topic>Pharmacology/Toxicology</topic><topic>Stem cells</topic><topic>Umbilical vein</topic><topic>Vascular endothelial growth factor</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mei, Shuya</creatorcontrib><creatorcontrib>Qin, Shaojie</creatorcontrib><creatorcontrib>Tang, Ri</creatorcontrib><creatorcontrib>Xu, Qiaoyi</creatorcontrib><creatorcontrib>Hu, Yue</creatorcontrib><creatorcontrib>Feng, Jinhua</creatorcontrib><creatorcontrib>He, Zhengyu</creatorcontrib><creatorcontrib>Gao, Yuan</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><creatorcontrib>Xing, Shunpeng</creatorcontrib><collection>CrossRef</collection><jtitle>Molecular & cellular toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mei, Shuya</au><au>Qin, Shaojie</au><au>Tang, Ri</au><au>Xu, Qiaoyi</au><au>Hu, Yue</au><au>Feng, Jinhua</au><au>He, Zhengyu</au><au>Gao, Yuan</au><au>Li, Hui</au><au>Xing, Shunpeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipopolysaccharide alters VEGF-A secretion of mesenchymal stem cells via the integrin β3-PI3K-AKT pathway</atitle><jtitle>Molecular & cellular toxicology</jtitle><stitle>Mol. Cell. Toxicol</stitle><date>2024</date><risdate>2024</risdate><volume>20</volume><issue>1</issue><spage>59</spage><epage>66</epage><pages>59-66</pages><issn>1738-642X</issn><eissn>2092-8467</eissn><abstract>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.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><doi>10.1007/s13273-022-00315-0</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4500-9888</orcidid><orcidid>https://orcid.org/0000-0002-2796-0832</orcidid></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Angiogenesis Biomedical and Life Sciences Cell Biology Endothelial cells Enzyme-linked immunosorbent assay Inflammation Life Sciences Lipopolysaccharides Mesenchymal stem cells Original Article Pharmacology/Toxicology Stem cells Umbilical vein Vascular endothelial growth factor Western blotting |
| title | Lipopolysaccharide alters VEGF-A secretion of mesenchymal stem cells via the integrin β3-PI3K-AKT pathway |
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