Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/β-catenin pathway
The therapeutic efficacy of umbilical cord mesenchymal stem cells (UCMSCs) in acute respiratory distress syndrome (ARDS) is mainly limited by the efficiency of homing of UCMSCs toward tissue damage. C-X-C chemokine receptor type 7 (CXCR7), which is involved in the mobilization of UCMSCs, is only exp...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223009150 |
| _version_ | 1797744090116259840 |
|---|---|
| author | Kun Xiao Chang Liu Heming Wang Fei Hou Yinghan Shi Zhi Rong Qian Hao Zhang David Y.B. Deng Lixin Xie |
| author_facet | Kun Xiao Chang Liu Heming Wang Fei Hou Yinghan Shi Zhi Rong Qian Hao Zhang David Y.B. Deng Lixin Xie |
| author_sort | Kun Xiao |
| collection | DOAJ |
| description | The therapeutic efficacy of umbilical cord mesenchymal stem cells (UCMSCs) in acute respiratory distress syndrome (ARDS) is mainly limited by the efficiency of homing of UCMSCs toward tissue damage. C-X-C chemokine receptor type 7 (CXCR7), which is involved in the mobilization of UCMSCs, is only expressed on the surface of a small proportion of UCMSCs. This study examined whether overexpression of CXCR7 in UCMSCs (UCMSCsOE-CXCR7) could improve their homing efficiency, and therefore, improve their effectiveness in fibrosis repair at the site of lung injury caused by ARDS. A lentiviral vector expressing CXCR7 was built and then transfect into UCMSCs. The impacts of CXCR7 expression of the proliferationand homing of UCMSCs were examined in a lipopolysaccharide-induced ARDS mouse model. The potential role and underlying mechanism of CXCR7 were examined by performing scratch assays, transwell assays, and immunoassays. The therapeutic dose and treatment time of UCMSCsOE-CXCR7 were directly proportional to their therapeutic effect on lung injury. In addition, overexpression of CXCR7 increased SDF-1-induced proliferation and migration of lung epithelial cells (Base-2b cells), and upregulation of CXCR7 inhibited α-SMA expression, suggesting that CXCR7 may have a role in alleviating pulmonary fibrosis caused by ARDS. Overexpression of CXCR7 in UCMSCs may improve their therapeutic effect of acute lung injury mouse, The mechanism of fibrosis repair by CXCR7 is inhibition of Jag1 via suppression of the Wnt/β-catenin pathway under the chemotaxis of SDF-1. |
| first_indexed | 2024-03-12T15:05:41Z |
| format | Article |
| id | doaj.art-c6ee9283531c433a8c3431ea2384b87d |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T15:05:41Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-c6ee9283531c433a8c3431ea2384b87d2023-08-13T04:52:40ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115124Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/β-catenin pathwayKun Xiao0Chang Liu1Heming Wang2Fei Hou3Yinghan Shi4Zhi Rong Qian5Hao Zhang6David Y.B. Deng7Lixin Xie8College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China; School of medicine Nankai university, Tianjin 300071, ChinaHainan Key Laboratory for Sustainable Utilization of Tropical Bioresource, Hainan University, Haikou 570228, ChinaCollege of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Scientific Research Center, The Seventh Affiliated Hospital of Sun YatSen University, Shenzhen 518106, China; Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou 350001, ChinaInstitute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China; Corresponding authors.Department of Scientific Research Center, The Seventh Affiliated Hospital of Sun YatSen University, Shenzhen 518106, China; Corresponding authors.College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China; Corresponding authors.The therapeutic efficacy of umbilical cord mesenchymal stem cells (UCMSCs) in acute respiratory distress syndrome (ARDS) is mainly limited by the efficiency of homing of UCMSCs toward tissue damage. C-X-C chemokine receptor type 7 (CXCR7), which is involved in the mobilization of UCMSCs, is only expressed on the surface of a small proportion of UCMSCs. This study examined whether overexpression of CXCR7 in UCMSCs (UCMSCsOE-CXCR7) could improve their homing efficiency, and therefore, improve their effectiveness in fibrosis repair at the site of lung injury caused by ARDS. A lentiviral vector expressing CXCR7 was built and then transfect into UCMSCs. The impacts of CXCR7 expression of the proliferationand homing of UCMSCs were examined in a lipopolysaccharide-induced ARDS mouse model. The potential role and underlying mechanism of CXCR7 were examined by performing scratch assays, transwell assays, and immunoassays. The therapeutic dose and treatment time of UCMSCsOE-CXCR7 were directly proportional to their therapeutic effect on lung injury. In addition, overexpression of CXCR7 increased SDF-1-induced proliferation and migration of lung epithelial cells (Base-2b cells), and upregulation of CXCR7 inhibited α-SMA expression, suggesting that CXCR7 may have a role in alleviating pulmonary fibrosis caused by ARDS. Overexpression of CXCR7 in UCMSCs may improve their therapeutic effect of acute lung injury mouse, The mechanism of fibrosis repair by CXCR7 is inhibition of Jag1 via suppression of the Wnt/β-catenin pathway under the chemotaxis of SDF-1.http://www.sciencedirect.com/science/article/pii/S0753332223009150Acute respiratory distress syndromeC-X-C chemokine receptor type 7Lung fibrosisUmbilical cord mesenchymal stem cellsHoming effect of stem cells |
| spellingShingle | Kun Xiao Chang Liu Heming Wang Fei Hou Yinghan Shi Zhi Rong Qian Hao Zhang David Y.B. Deng Lixin Xie Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/β-catenin pathway Biomedicine & Pharmacotherapy Acute respiratory distress syndrome C-X-C chemokine receptor type 7 Lung fibrosis Umbilical cord mesenchymal stem cells Homing effect of stem cells |
| title | Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/β-catenin pathway |
| title_full | Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/β-catenin pathway |
| title_fullStr | Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/β-catenin pathway |
| title_full_unstemmed | Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/β-catenin pathway |
| title_short | Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/β-catenin pathway |
| title_sort | umbilical cord mesenchymal stem cells overexpressing cxcr7 facilitate treatment of ards associated pulmonary fibrosis via inhibition of notch jag1 mediated by the wnt β catenin pathway |
| topic | Acute respiratory distress syndrome C-X-C chemokine receptor type 7 Lung fibrosis Umbilical cord mesenchymal stem cells Homing effect of stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223009150 |
| work_keys_str_mv | AT kunxiao umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway AT changliu umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway AT hemingwang umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway AT feihou umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway AT yinghanshi umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway AT zhirongqian umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway AT haozhang umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway AT davidybdeng umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway AT lixinxie umbilicalcordmesenchymalstemcellsoverexpressingcxcr7facilitatetreatmentofardsassociatedpulmonaryfibrosisviainhibitionofnotchjag1mediatedbythewntbcateninpathway |