Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization
Summary: Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated adipose-derived extracellular matrix (Ad-ECM) as a mitigator of RISF. Female C57BL/6J mice that were irradiated developed fibrosis, whic...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223017376 |
| _version_ | 1797729867552260096 |
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| author | Somaiah Chinnapaka Katherine S. Yang Yusuf Surucu Fuat B. Bengur José A. Arellano Zayaan Tirmizi Hamid Malekzadeh Michael W. Epperly Wen Hou Joel S. Greenberger J. Peter Rubin Asim Ejaz |
| author_facet | Somaiah Chinnapaka Katherine S. Yang Yusuf Surucu Fuat B. Bengur José A. Arellano Zayaan Tirmizi Hamid Malekzadeh Michael W. Epperly Wen Hou Joel S. Greenberger J. Peter Rubin Asim Ejaz |
| author_sort | Somaiah Chinnapaka |
| collection | DOAJ |
| description | Summary: Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated adipose-derived extracellular matrix (Ad-ECM) as a mitigator of RISF. Female C57BL/6J mice that were irradiated developed fibrosis, which was mitigated by a single local Ad-ECM injection, improving limb movement and reducing epithelium thickness and collagen deposition. Ad-ECM treatment resulted in decreased expression of pro-inflammatory and fibrotic genes, and upregulation of anti-inflammatory cytokines, promoting M2 macrophage polarization. Co-culture of irradiated human fibroblasts with Ad-ECM down-modulated fibrotic gene expression and enhanced bone marrow cell migration. Ad-ECM treatment also increased interleukin (IL)-4, IL-5, and IL-15 expression in endothelial cells, stimulating M2 macrophage polarization and alleviating RISF. Prophylactic use of Ad-ECM showed effectiveness in mitigation. This study suggests Ad-ECM’s potential in treating chronic-stage fibrosis. |
| first_indexed | 2024-03-12T11:35:54Z |
| format | Article |
| id | doaj.art-d0e04c23d33743148cafa71d07da7464 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T11:35:54Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d0e04c23d33743148cafa71d07da74642023-09-01T05:02:57ZengElsevieriScience2589-00422023-09-01269107660Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarizationSomaiah Chinnapaka0Katherine S. Yang1Yusuf Surucu2Fuat B. Bengur3José A. Arellano4Zayaan Tirmizi5Hamid Malekzadeh6Michael W. Epperly7Wen Hou8Joel S. Greenberger9J. Peter Rubin10Asim Ejaz11Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USADepartment of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA; Corresponding authorSummary: Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated adipose-derived extracellular matrix (Ad-ECM) as a mitigator of RISF. Female C57BL/6J mice that were irradiated developed fibrosis, which was mitigated by a single local Ad-ECM injection, improving limb movement and reducing epithelium thickness and collagen deposition. Ad-ECM treatment resulted in decreased expression of pro-inflammatory and fibrotic genes, and upregulation of anti-inflammatory cytokines, promoting M2 macrophage polarization. Co-culture of irradiated human fibroblasts with Ad-ECM down-modulated fibrotic gene expression and enhanced bone marrow cell migration. Ad-ECM treatment also increased interleukin (IL)-4, IL-5, and IL-15 expression in endothelial cells, stimulating M2 macrophage polarization and alleviating RISF. Prophylactic use of Ad-ECM showed effectiveness in mitigation. This study suggests Ad-ECM’s potential in treating chronic-stage fibrosis.http://www.sciencedirect.com/science/article/pii/S2589004223017376Cell biologyDermatologyFibrosisImmunologyStem cells research |
| spellingShingle | Somaiah Chinnapaka Katherine S. Yang Yusuf Surucu Fuat B. Bengur José A. Arellano Zayaan Tirmizi Hamid Malekzadeh Michael W. Epperly Wen Hou Joel S. Greenberger J. Peter Rubin Asim Ejaz Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization iScience Cell biology Dermatology Fibrosis Immunology Stem cells research |
| title | Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization |
| title_full | Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization |
| title_fullStr | Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization |
| title_full_unstemmed | Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization |
| title_short | Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization |
| title_sort | human adipose ecm alleviates radiation induced skin fibrosis via endothelial cell mediated m2 macrophage polarization |
| topic | Cell biology Dermatology Fibrosis Immunology Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223017376 |
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