The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment Approaches
Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disease characterized by the loss or dysfunction of collagen VII, predisposing patients to dermal–epidermal separation. This disease is highly associated with the development of progressive fibrosis of the skin and other organs an...
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Elsevier
2025-05-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026725000074 |
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| author | Alexander Nyström Celine Pattaroni Johannes S. Kern |
| author_facet | Alexander Nyström Celine Pattaroni Johannes S. Kern |
| author_sort | Alexander Nyström |
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| description | Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disease characterized by the loss or dysfunction of collagen VII, predisposing patients to dermal–epidermal separation. This disease is highly associated with the development of progressive fibrosis of the skin and other organs and the occurrence of lethal cutaneous squamous cell carcinomas (cSCCs). These are not only caused by chronic wounding but also by collagen VII deficiency, which may directly alter cellular responses. This review focuses on the role of fibroblasts in DEB pathogenesis. In addition to keratinocytes, fibroblasts contribute to collagen VII production. Fibroblasts in injured DEB skin are activated and profibrotic and have a propensity to alter tissue homeostasis. Disease progression in DEB follows the trajectory of cancer injury through inflammation and fibrosis. Fibroblast activation and extracellular matrix remodeling that occur in advancing DEB may be directly linked to the aggressive biological behavior of DEB cSCCs. In contrast, the mechanisms underlying chronic itching and pain in DEB and the potential contribution of fibroblasts to these symptoms are only partially understood. The first therapies for DEB recently received regulatory approval, which is a major milestone toward a cure. However, to successfully treat DEB, systemic therapies to mitigate chronic inflammation and fibrosis are likely required, in addition to local collagen VII replacement. |
| format | Article |
| id | doaj-art-3fe3ad212cfc4a1eb555bcc41a0e9b87 |
| institution | Kabale University |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
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| series | JID Innovations |
| spelling | doaj-art-3fe3ad212cfc4a1eb555bcc41a0e9b872025-08-20T03:49:41ZengElsevierJID Innovations2667-02672025-05-015310035310.1016/j.xjidi.2025.100353The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment ApproachesAlexander Nyström0Celine Pattaroni1Johannes S. Kern2Department of Dermatology, Medical Faculty, Medical Center - University of Freiburg, Freiburg, Germany; Correspondence: Alexander Nyström, Department of Dermatology, Faculty of Medicine, Medical Center – University of Freiburg, Hauptstrasse 7, Freiburg 79140, Germany.Department of Immunology, The School of Translational Medicine, Monash University, Melbourne, AustraliaDepartment of Dermatology, Alfred Health, Melbourne, Australia; Department of Medicine, The School of Translational Medicine, Monash University, Melbourne, Australia; Medicine - Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia; Johannes S. Kern, Department of Dermatology, Alfred Health, 55 Commercial Rd, Melbourne, VIC 3004, Australia.Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disease characterized by the loss or dysfunction of collagen VII, predisposing patients to dermal–epidermal separation. This disease is highly associated with the development of progressive fibrosis of the skin and other organs and the occurrence of lethal cutaneous squamous cell carcinomas (cSCCs). These are not only caused by chronic wounding but also by collagen VII deficiency, which may directly alter cellular responses. This review focuses on the role of fibroblasts in DEB pathogenesis. In addition to keratinocytes, fibroblasts contribute to collagen VII production. Fibroblasts in injured DEB skin are activated and profibrotic and have a propensity to alter tissue homeostasis. Disease progression in DEB follows the trajectory of cancer injury through inflammation and fibrosis. Fibroblast activation and extracellular matrix remodeling that occur in advancing DEB may be directly linked to the aggressive biological behavior of DEB cSCCs. In contrast, the mechanisms underlying chronic itching and pain in DEB and the potential contribution of fibroblasts to these symptoms are only partially understood. The first therapies for DEB recently received regulatory approval, which is a major milestone toward a cure. However, to successfully treat DEB, systemic therapies to mitigate chronic inflammation and fibrosis are likely required, in addition to local collagen VII replacement.http://www.sciencedirect.com/science/article/pii/S2667026725000074Collagen VIIcSCCExtracellular matrixSkin fibrosisTissue homeostasis |
| spellingShingle | Alexander Nyström Celine Pattaroni Johannes S. Kern The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment Approaches JID Innovations Collagen VII cSCC Extracellular matrix Skin fibrosis Tissue homeostasis |
| title | The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment Approaches |
| title_full | The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment Approaches |
| title_fullStr | The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment Approaches |
| title_full_unstemmed | The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment Approaches |
| title_short | The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment Approaches |
| title_sort | role of fibroblasts in dystrophic epidermolysis bullosa pathogenesis and current treatment approaches |
| topic | Collagen VII cSCC Extracellular matrix Skin fibrosis Tissue homeostasis |
| url | http://www.sciencedirect.com/science/article/pii/S2667026725000074 |
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