Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids
Background: Keloid is a disease caused by abnormal proliferation of skin fibres, the causative mechanism of which remains unclear.Method: In this study, endothelial cells of keloids were studied using scRNAseq combined with bulk-RNAseq data from keloids. The master regulators driving keloid developm...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.917726/full |
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| author | Delin Liu Delin Liu Yidi Zhang Lisha Zhen Lisha Zhen Rong Xu Zhenling Ji Zheng Ye |
| author_facet | Delin Liu Delin Liu Yidi Zhang Lisha Zhen Lisha Zhen Rong Xu Zhenling Ji Zheng Ye |
| author_sort | Delin Liu |
| collection | DOAJ |
| description | Background: Keloid is a disease caused by abnormal proliferation of skin fibres, the causative mechanism of which remains unclear.Method: In this study, endothelial cells of keloids were studied using scRNAseq combined with bulk-RNAseq data from keloids. The master regulators driving keloid development were identified by transcription factor enrichment analysis. The pattern of changes in vascular endothelial cells during keloid development was explored by inferring endothelial cell differentiation trajectories. Deconvolution of bulkRNAseq by CIBERSORTX verified the pattern of keloidogenesis. Immunohistochemistry for verification of the lesion process in keloid endothelial cells.Results: The endothelial cells of keloids consist of four main cell populations (MMP1+ Endo0, FOS + JUN + Endo1, IL6+CSF3+Endo2, CXCL12 + Endo3). Endo3 is an endothelial progenitor cell, Endo1 is an endothelial cell in the resting state, Endo2 is an endothelial cell in the activated state and Endo0 is an endothelial cell in the terminally differentiated state. Activation of the NFΚB signaling pathway is a typical feature of Endo2 and represents the early skin state of keloids.Conclusion: We have identified patterns of vascular endothelial cell lesions during keloidogenesis and development, and have found that activation of the NFΚB signaling pathway is an essential feature of keloid formation. These findings are expected to contribute to the understanding of the pathogenesis of keloids and to the development of new targeted therapeutic agents for the lesional characteristics of vascular endothelial cells. |
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| language | English |
| last_indexed | 2024-04-12T00:12:14Z |
| publishDate | 2022-08-01 |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-083f5bf6cd984522a78c04403c2cc6b72022-12-22T03:55:56ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-08-011010.3389/fbioe.2022.917726917726Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloidsDelin Liu0Delin Liu1Yidi Zhang2Lisha Zhen3Lisha Zhen4Rong Xu5Zhenling Ji6Zheng Ye7Department of General Surgery, Institute for Minimally Invasive Surgery, Affiliated Zhongda Hospital, Medical School, Southeast University, Nanjing, ChinaDepartment of Endcrinology, Affiliated Zhongda Hospital, Medical School, Southeast University, Nanjing, ChinaDepartment of Endcrinology, Affiliated Zhongda Hospital, Medical School, Southeast University, Nanjing, ChinaSchool of Statistics, Renmin University of China, Beijing, ChinaBeijing Sankuai Online Technology Co.,Ltd, Dhaka, BangladeshDepartment of Endcrinology, Affiliated Zhongda Hospital, Medical School, Southeast University, Nanjing, ChinaDepartment of General Surgery, Institute for Minimally Invasive Surgery, Affiliated Zhongda Hospital, Medical School, Southeast University, Nanjing, ChinaDepartment of Endcrinology, Affiliated Zhongda Hospital, Medical School, Southeast University, Nanjing, ChinaBackground: Keloid is a disease caused by abnormal proliferation of skin fibres, the causative mechanism of which remains unclear.Method: In this study, endothelial cells of keloids were studied using scRNAseq combined with bulk-RNAseq data from keloids. The master regulators driving keloid development were identified by transcription factor enrichment analysis. The pattern of changes in vascular endothelial cells during keloid development was explored by inferring endothelial cell differentiation trajectories. Deconvolution of bulkRNAseq by CIBERSORTX verified the pattern of keloidogenesis. Immunohistochemistry for verification of the lesion process in keloid endothelial cells.Results: The endothelial cells of keloids consist of four main cell populations (MMP1+ Endo0, FOS + JUN + Endo1, IL6+CSF3+Endo2, CXCL12 + Endo3). Endo3 is an endothelial progenitor cell, Endo1 is an endothelial cell in the resting state, Endo2 is an endothelial cell in the activated state and Endo0 is an endothelial cell in the terminally differentiated state. Activation of the NFΚB signaling pathway is a typical feature of Endo2 and represents the early skin state of keloids.Conclusion: We have identified patterns of vascular endothelial cell lesions during keloidogenesis and development, and have found that activation of the NFΚB signaling pathway is an essential feature of keloid formation. These findings are expected to contribute to the understanding of the pathogenesis of keloids and to the development of new targeted therapeutic agents for the lesional characteristics of vascular endothelial cells.https://www.frontiersin.org/articles/10.3389/fbioe.2022.917726/fullkeloidIL6endothelial cells (ECs)scRNAseqNFkB (RelA) |
| spellingShingle | Delin Liu Delin Liu Yidi Zhang Lisha Zhen Lisha Zhen Rong Xu Zhenling Ji Zheng Ye Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids Frontiers in Bioengineering and Biotechnology keloid IL6 endothelial cells (ECs) scRNAseq NFkB (RelA) |
| title | Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids |
| title_full | Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids |
| title_fullStr | Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids |
| title_full_unstemmed | Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids |
| title_short | Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids |
| title_sort | activation of the nfκb signaling pathway in il6 csf3 vascular endothelial cells promotes the formation of keloids |
| topic | keloid IL6 endothelial cells (ECs) scRNAseq NFkB (RelA) |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.917726/full |
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