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
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Published:2023-10-12
Issue:10
Volume:21
Page:531
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ISSN:1660-3397
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Container-title:Marine Drugs
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language:en
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Short-container-title:Marine Drugs
Author:
Lee Do Young12, Song Won Hoon23ORCID, Lim Ye Seon12ORCID, Lee Changyong12, Rajbongshi Lata12, Hwang Seon Yeong12ORCID, Kim Byoung Soo4ORCID, Lee Dongjun5ORCID, Song Yong Jung26, Kim Hwi-Gon26, Yoon Sik12ORCID
Affiliation:
1. Department of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 626-870, Republic of Korea 2. Immune Reconstitution Research Center of Medical Research Institute, Pusan National University College of Medicine, Yangsan 626-870, Republic of Korea 3. Department of Urology, Pusan National University Yangsan Hospital and Pusan National University College of Medicine, Yangsan 626-870, Republic of Korea 4. School of Biomedical Convergence Engineering, Pusan National University, Yangsan 626-870, Republic of Korea 5. Department of Convergence Medicine, Pusan National University College of Medicine, Yangsan 626-870, Republic of Korea 6. Department of Obstetrics and Gynecology, Pusan National University Yangsan Hospital and Pusan National University College of Medicine, Yangsan 626-870, Republic of Korea
Abstract
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.
Funder
National Research Foundation of Korea Pusan National University Research Grant
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science
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