1. Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling
- Author
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Joonsuk Bae, Seung Min Nam, Sun-Jae Lee, Sung Sik Hur, Hyunbum Kim, Laurensia Danis Anggradita, Nathaniel S. Hwang, and Yongsung Hwang
- 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 - 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.
- Published
- 2021