Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4
Mesenchymal stem cells (MSCs) can attract host endothelial progenitor cells (EPCs) to promote vascularization in tissue-engineered constructs (TECs). Nevertheless, the underlying mechanism remains vague. This study is aimed at investigating the roles of CXCR2 and CXCR4 in the EPC migration towards M...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/4197164 |
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| author | Yingyun Tan Linjing Shu Peng Xu Shi Bai |
| author_facet | Yingyun Tan Linjing Shu Peng Xu Shi Bai |
| author_sort | Yingyun Tan |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) can attract host endothelial progenitor cells (EPCs) to promote vascularization in tissue-engineered constructs (TECs). Nevertheless, the underlying mechanism remains vague. This study is aimed at investigating the roles of CXCR2 and CXCR4 in the EPC migration towards MSCs. In vitro, Transwell assays were performed to evaluate the migration of EPCs towards MSCs. Antagonists and shRNAs targeting CXCR2, CXCR4, and JAK/STAT3 were applied for the signaling blockade. Western blot and RT-PCR were conducted to analyze the molecular events in EPCs. In vivo, TECs were constructed and subcutaneously implanted into GFP+ transgenic mice. Signaling inhibitors were injected in an orientated manner into TECs. Recruitment of host CD34+ cells was evaluated by immunofluorescence. Eventually, we demonstrated that CXCR2 and CXCR4 were both highly expressed in migrated EPCs and indispensable for MSC-induced EPC migration. CXCR2 and CXCR4 strongly correlated with each other in the way that the expression of CXCR2 and CXCR2-mediated migration depends on the activity of CXCR4 and vice versa. Further studies documented that both of CXCR2 and CXCR4 activated STAT3 signaling, which in turn regulated the expression of CXCR2 and CXCR4, as well as cell migration. In summary, we firstly introduced a reciprocal crosstalk between CXCR2 and CXCR4 in the context of EPC migration. This feedback loop plays critical roles in the migration of EPCs towards MSCs. |
| format | Article |
| id | doaj-art-3ffd3326d7504a0a8a5b8a11f5401ad5 |
| institution | DOAJ |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-3ffd3326d7504a0a8a5b8a11f5401ad52025-08-20T02:39:12ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/41971644197164Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4Yingyun Tan0Linjing Shu1Peng Xu2Shi Bai3Stomatological Hospital of Chongqing Medical University, Chongqing, ChinaStomatological Hospital of Chongqing Medical University, Chongqing, ChinaStomatological Hospital of Chongqing Medical University, Chongqing, ChinaStomatological Hospital of Chongqing Medical University, Chongqing, ChinaMesenchymal stem cells (MSCs) can attract host endothelial progenitor cells (EPCs) to promote vascularization in tissue-engineered constructs (TECs). Nevertheless, the underlying mechanism remains vague. This study is aimed at investigating the roles of CXCR2 and CXCR4 in the EPC migration towards MSCs. In vitro, Transwell assays were performed to evaluate the migration of EPCs towards MSCs. Antagonists and shRNAs targeting CXCR2, CXCR4, and JAK/STAT3 were applied for the signaling blockade. Western blot and RT-PCR were conducted to analyze the molecular events in EPCs. In vivo, TECs were constructed and subcutaneously implanted into GFP+ transgenic mice. Signaling inhibitors were injected in an orientated manner into TECs. Recruitment of host CD34+ cells was evaluated by immunofluorescence. Eventually, we demonstrated that CXCR2 and CXCR4 were both highly expressed in migrated EPCs and indispensable for MSC-induced EPC migration. CXCR2 and CXCR4 strongly correlated with each other in the way that the expression of CXCR2 and CXCR2-mediated migration depends on the activity of CXCR4 and vice versa. Further studies documented that both of CXCR2 and CXCR4 activated STAT3 signaling, which in turn regulated the expression of CXCR2 and CXCR4, as well as cell migration. In summary, we firstly introduced a reciprocal crosstalk between CXCR2 and CXCR4 in the context of EPC migration. This feedback loop plays critical roles in the migration of EPCs towards MSCs.http://dx.doi.org/10.1155/2019/4197164 |
| spellingShingle | Yingyun Tan Linjing Shu Peng Xu Shi Bai Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4 Stem Cells International |
| title | Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4 |
| title_full | Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4 |
| title_fullStr | Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4 |
| title_full_unstemmed | Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4 |
| title_short | Mesenchymal Stem Cells Attract Endothelial Progenitor Cells via a Positive Feedback Loop between CXCR2 and CXCR4 |
| title_sort | mesenchymal stem cells attract endothelial progenitor cells via a positive feedback loop between cxcr2 and cxcr4 |
| url | http://dx.doi.org/10.1155/2019/4197164 |
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