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Open AccessArticle

Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling

1
Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea
2
School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Korea
3
Department of Integrated Biomedical Science, Soonchunhyang University, Asan-si 31538, Korea
4
Department of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si 14584, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this study.
Academic Editor: Serena Lembo
Int. J. Mol. Sci. 2021, 22(4), 2198; https://doi.org/10.3390/ijms22042198
Received: 8 January 2021 / Revised: 18 February 2021 / Accepted: 20 February 2021 / Published: 23 February 2021
(This article belongs to the Special Issue Skin Inflammation Aging and Diseases)
Keloid and hypertrophic scars are skin fibrosis-associated disorders that exhibit an uncontrollable proliferation of fibroblasts and their subsequent contribution to the excessive accumulation of extracellular matrix (ECM) in the dermis. In this study, to elucidate the underlying mechanisms, we investigated the pivotal roles of epidermal growth factor (EGF) in modulating fibrotic phenotypes of keloid and hypertrophic dermal fibroblasts. Our initial findings revealed the molecular signatures of keloid dermal fibroblasts and showed the highest degree of skin fibrosis markers, ECM remodeling, anabolic collagen-cross-linking enzymes, such as lysyl oxidase (LOX) and four LOX-like family enzymes, migration ability, and cell–matrix traction force, at cell–matrix interfaces. Furthermore, we observed significant EGF-mediated downregulation of anabolic collagen-cross-linking enzymes, resulting in amelioration of fibrotic phenotypes and a decrease in cell motility measured according to the cell–matrix traction force. These findings offer insight into the important roles of EGF-mediated cell–matrix interactions at the cell–matrix interface, as well as ECM remodeling. Furthermore, the results suggest their contribution to the reduction of fibrotic phenotypes in keloid dermal fibroblasts, which could lead to the development of therapeutic modalities to prevent or reduce scar tissue formation. View Full-Text
Keywords: keloid scar; hypertrophic scar; dermal fibroblast; epidermal growth factor; ECM remodeling; traction force keloid scar; hypertrophic scar; dermal fibroblast; epidermal growth factor; ECM remodeling; traction force
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MDPI and ACS Style

Kim, H.; Anggradita, L.D.; Lee, S.-J.; Hur, S.S.; Bae, J.; Hwang, N.S.-Y.; Nam, S.M.; Hwang, Y. Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling. Int. J. Mol. Sci. 2021, 22, 2198. https://doi.org/10.3390/ijms22042198

AMA Style

Kim H, Anggradita LD, Lee S-J, Hur SS, Bae J, Hwang NS-Y, Nam SM, Hwang Y. Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling. International Journal of Molecular Sciences. 2021; 22(4):2198. https://doi.org/10.3390/ijms22042198

Chicago/Turabian Style

Kim, Hyunbum; Anggradita, Laurensia D.; Lee, Sun-Jae; Hur, Sung S.; Bae, Joonsuk; Hwang, Nathaniel S.-Y.; Nam, Seung M.; Hwang, Yongsung. 2021. "Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling" Int. J. Mol. Sci. 22, no. 4: 2198. https://doi.org/10.3390/ijms22042198

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