Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models
Abstract Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at path...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10630 |
| _version_ | 1797289301216591872 |
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| author | Yaxin Tan Mengde Zhang Yi Kong Fanliang Zhang Yuzhen Wang Yuyan Huang Wei Song Zhao Li Linhao Hou Liting Liang Xu Guo Qinghua Liu Yu Feng Chao Zhang Xiaobing Fu Sha Huang |
| author_facet | Yaxin Tan Mengde Zhang Yi Kong Fanliang Zhang Yuzhen Wang Yuyan Huang Wei Song Zhao Li Linhao Hou Liting Liang Xu Guo Qinghua Liu Yu Feng Chao Zhang Xiaobing Fu Sha Huang |
| author_sort | Yaxin Tan |
| collection | DOAJ |
| description | Abstract Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co‐culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF‐β. Additionally, a suspended co‐culture multicellular spheroid model revealed molecular‐level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro‐angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF‐β, IL‐17, Wnt, Notch, PI3K‐Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts‐endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases. |
| first_indexed | 2024-03-07T19:02:59Z |
| format | Article |
| id | doaj.art-029d08606cd9411980d835753a8d2e66 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-03-07T19:02:59Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-029d08606cd9411980d835753a8d2e662024-03-01T11:14:07ZengWileyBioengineering & Translational Medicine2380-67612024-03-0192n/an/a10.1002/btm2.10630Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo modelsYaxin Tan0Mengde Zhang1Yi Kong2Fanliang Zhang3Yuzhen Wang4Yuyan Huang5Wei Song6Zhao Li7Linhao Hou8Liting Liang9Xu Guo10Qinghua Liu11Yu Feng12Chao Zhang13Xiaobing Fu14Sha Huang15College of Graduate Tianjin Medical University Tianjin PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaCollege of Graduate Tianjin Medical University Tianjin PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaCollege of Graduate Tianjin Medical University Tianjin PR ChinaResearch Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing PR ChinaAbstract Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co‐culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF‐β. Additionally, a suspended co‐culture multicellular spheroid model revealed molecular‐level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro‐angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF‐β, IL‐17, Wnt, Notch, PI3K‐Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts‐endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases.https://doi.org/10.1002/btm2.10630cell crosstalkendothelial cellfibroblastscar formationspheroids |
| spellingShingle | Yaxin Tan Mengde Zhang Yi Kong Fanliang Zhang Yuzhen Wang Yuyan Huang Wei Song Zhao Li Linhao Hou Liting Liang Xu Guo Qinghua Liu Yu Feng Chao Zhang Xiaobing Fu Sha Huang Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models Bioengineering & Translational Medicine cell crosstalk endothelial cell fibroblast scar formation spheroids |
| title | Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models |
| title_full | Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models |
| title_fullStr | Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models |
| title_full_unstemmed | Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models |
| title_short | Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models |
| title_sort | fibroblasts and endothelial cells interplay drives hypertrophic scar formation insights from in vitro and in vivo models |
| topic | cell crosstalk endothelial cell fibroblast scar formation spheroids |
| url | https://doi.org/10.1002/btm2.10630 |
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