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Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 4, International Journal of Molecular Sciences, Vol 22, Iss 2198, p 2198 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
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.
- Subjects :
- Male
0301 basic medicine
lcsh:Chemistry
Extracellular matrix
030207 dermatology & venereal diseases
ECM remodeling
0302 clinical medicine
Keloid
keloid scar
Cell Movement
Epidermal growth factor
Fibrosis
dermal fibroblast
lcsh:QH301-705.5
Cells, Cultured
Spectroscopy
Skin
integumentary system
Chemistry
Hydrogels
General Medicine
hypertrophic scar
Middle Aged
Enzymes
Extracellular Matrix
Computer Science Applications
Cell biology
medicine.anatomical_structure
epidermal growth factor
Female
Adult
Cicatrix, Hypertrophic
traction force
Lysyl oxidase
Catalysis
Article
Inorganic Chemistry
Dermal fibroblast
03 medical and health sciences
Hypertrophic scar
Dermis
Elastic Modulus
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Organic Chemistry
Fibroblasts
medicine.disease
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 22
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....8481087109999d22c84aaa76a29f44fa