Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodelingopen access
- Authors
- Kim, Hyunbum; Anggradita, Laurensia Danis; Lee, Sun-Jae; Hur, Sung Sik; Bae, Joonsuk; Hwang, Nathaniel Suk-Yeon; Nam, Seung Min; Hwang, Yongsung
- Issue Date
- Feb-2021
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- keloid scar; hypertrophic scar; dermal fibroblast; epidermal growth factor; ECM remodeling; traction force
- Citation
- International Journal of Molecular Sciences, v.22, no.4
- Journal Title
- International Journal of Molecular Sciences
- Volume
- 22
- Number
- 4
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/2057
- DOI
- 10.3390/ijms22042198
- ISSN
- 1661-6596
1422-0067
- Abstract
- 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.
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- Appears in
Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
- College of Medicine > Department of Plastic Surgery > 1. Journal Articles
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