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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/21/10/531
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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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