Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling
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 inve...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/2198 |
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| author | Hyunbum Kim Laurensia Danis Anggradita Sun-Jae Lee Sung Sik Hur Joonsuk Bae Nathaniel Suk-Yeon Hwang Seung Min Nam Yongsung Hwang |
| author_facet | Hyunbum Kim Laurensia Danis Anggradita Sun-Jae Lee Sung Sik Hur Joonsuk Bae Nathaniel Suk-Yeon Hwang Seung Min Nam Yongsung Hwang |
| author_sort | Hyunbum Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T00:37:27Z |
| format | Article |
| id | doaj.art-60a13d29052b4fc2b51b02edc5a8180e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:37:27Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-60a13d29052b4fc2b51b02edc5a8180e2023-12-11T18:05:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224219810.3390/ijms22042198Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix RemodelingHyunbum Kim0Laurensia Danis Anggradita1Sun-Jae Lee2Sung Sik Hur3Joonsuk Bae4Nathaniel Suk-Yeon Hwang5Seung Min Nam6Yongsung Hwang7Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, KoreaDepartment of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si 14584, KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, KoreaDepartment of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si 14584, KoreaSchool of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, KoreaDepartment of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si 14584, KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, KoreaKeloid 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.https://www.mdpi.com/1422-0067/22/4/2198keloid scarhypertrophic scardermal fibroblastepidermal growth factorECM remodelingtraction force |
| spellingShingle | Hyunbum Kim Laurensia Danis Anggradita Sun-Jae Lee Sung Sik Hur Joonsuk Bae Nathaniel Suk-Yeon Hwang Seung Min Nam Yongsung Hwang Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling International Journal of Molecular Sciences keloid scar hypertrophic scar dermal fibroblast epidermal growth factor ECM remodeling traction force |
| title | Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling |
| title_full | Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling |
| title_fullStr | Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling |
| title_full_unstemmed | Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling |
| title_short | Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling |
| title_sort | ameliorating fibrotic phenotypes of keloid dermal fibroblasts through an epidermal growth factor mediated extracellular matrix remodeling |
| topic | keloid scar hypertrophic scar dermal fibroblast epidermal growth factor ECM remodeling traction force |
| url | https://www.mdpi.com/1422-0067/22/4/2198 |
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