Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury
Prolonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing...
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MDPI AG
2023-10-01
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author | Do Young Lee Won Hoon Song Ye Seon Lim Changyong Lee Lata Rajbongshi Seon Yeong Hwang Byoung Soo Kim Dongjun Lee Yong Jung Song Hwi-Gon Kim Sik Yoon |
author_facet | Do Young Lee Won Hoon Song Ye Seon Lim Changyong Lee Lata Rajbongshi Seon Yeong Hwang Byoung Soo Kim Dongjun Lee Yong Jung Song Hwi-Gon Kim Sik Yoon |
author_sort | Do Young Lee |
collection | DOAJ |
description | Prolonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing therapeutic interventions to revert immune suppression in immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities of thymic epithelial cells (TECs), including cell proliferation, thymocyte adhesion, and the gene expression of thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTβ, IL-22R, RANK, LTβR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, and CK8 through the NF-κB signal transduction pathway. Furthermore, our study also revealed the cytoprotective effects of FCPs on TECs against cyclophosphamide-induced cellular injury through the NF-κB signaling pathway. Importantly, FCPs exhibited a significant capability to facilitate thymic regeneration in mice after cyclophosphamide-induced damage via the NF-κB pathway. Taken together, this study sheds light on the role of FCPs in TEC function, thymopoiesis, and thymic regeneration, providing greater insight into the development of novel therapeutic strategies for effective thymus repopulation for numerous clinical conditions in which immune reconstitution is required. |
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spelling | doaj.art-772e10362a4d4960a6bf93d00f31db8f2023-11-19T17:09:33ZengMDPI AGMarine Drugs1660-33972023-10-01211053110.3390/md21100531Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced InjuryDo Young Lee0Won Hoon Song1Ye Seon Lim2Changyong Lee3Lata Rajbongshi4Seon Yeong Hwang5Byoung Soo Kim6Dongjun Lee7Yong Jung Song8Hwi-Gon Kim9Sik Yoon10Department of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaImmune Reconstitution Research Center of Medical Research Institute, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaDepartment of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaDepartment of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaDepartment of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaDepartment of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaSchool of Biomedical Convergence Engineering, Pusan National University, Yangsan 626-870, Republic of KoreaDepartment of Convergence Medicine, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaImmune Reconstitution Research Center of Medical Research Institute, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaImmune Reconstitution Research Center of Medical Research Institute, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaDepartment of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 626-870, Republic of KoreaProlonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing therapeutic interventions to revert immune suppression in immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities of thymic epithelial cells (TECs), including cell proliferation, thymocyte adhesion, and the gene expression of thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTβ, IL-22R, RANK, LTβR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, and CK8 through the NF-κB signal transduction pathway. Furthermore, our study also revealed the cytoprotective effects of FCPs on TECs against cyclophosphamide-induced cellular injury through the NF-κB signaling pathway. Importantly, FCPs exhibited a significant capability to facilitate thymic regeneration in mice after cyclophosphamide-induced damage via the NF-κB pathway. Taken together, this study sheds light on the role of FCPs in TEC function, thymopoiesis, and thymic regeneration, providing greater insight into the development of novel therapeutic strategies for effective thymus repopulation for numerous clinical conditions in which immune reconstitution is required.https://www.mdpi.com/1660-3397/21/10/531fish collagen peptidesthymusthymic epithelial cellsthymic regenerationthymopoietic factorNF-κB pathway |
spellingShingle | Do Young Lee Won Hoon Song Ye Seon Lim Changyong Lee Lata Rajbongshi Seon Yeong Hwang Byoung Soo Kim Dongjun Lee Yong Jung Song Hwi-Gon Kim Sik Yoon Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury Marine Drugs fish collagen peptides thymus thymic epithelial cells thymic regeneration thymopoietic factor NF-κB pathway |
title | Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury |
title_full | Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury |
title_fullStr | Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury |
title_full_unstemmed | Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury |
title_short | Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury |
title_sort | fish collagen peptides enhance thymopoietic gene expression cell proliferation thymocyte adherence and cytoprotection in thymic epithelial cells via activation of the nuclear factor κb pathway leading to thymus regeneration after cyclophosphamide induced injury |
topic | fish collagen peptides thymus thymic epithelial cells thymic regeneration thymopoietic factor NF-κB pathway |
url | https://www.mdpi.com/1660-3397/21/10/531 |
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