Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden

Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely...

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Bibliographic Details
Published in:Acta dermato-venereologica 2023-04, Vol.103, p.adv4475-adv4475
Main Authors: Darmawan, Claudia C, Hur, Keunyoung, Kusumaningrum, Novi, Chung, Jin Ho, Lee, Si-Hyung, Mun, Je-Ho
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Cellular Senescence
Dasatinib - metabolism
Dasatinib - pharmacology
Dasatinib - therapeutic use
Fibroblasts - metabolism
Fibroblasts - pathology
fibrosis
keloid
Keloid - drug therapy
Keloid - metabolism
Keloid - pathology
Mice
Original
Procollagen - metabolism
Procollagen - pharmacology
senotherapeutics
therapeutics
therapy
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Summary:Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely unknown. This study investigated senescent fibroblasts in keloids and assessed the effects of dasatinib on these cells. Tissues acquired from keloid removal surgery were analysed for senescence-associated β-galactosidase-positive cells, p16 expression, and the effects of dasatinib treatment on keloids. Keloid tissue was xenotransplanted into mice, and the effect of intralesional dasatinib injection on keloid growth was observed. The results showed that the numbers of β-galactosidase-positive and p16-expressing cells were higher in the keloids compared with in the controls. Dasatinib induced selective clearance of senescent cells and decreased procollagen expression in cultured keloid fibroblasts. In this xenotransplant keloid mouse model, intralesional injection of dasatinib reduced gross keloid tissue weight and the expression of both procollagen and p16. In addition, dasatinib-treated keloid fibroblasts conditioned medium reduced procollagen and p16 expression in cultured keloid fibroblasts. In conclusion, these results suggest that an increased number of senescent fibroblasts may play an important role in the pathogenesis of keloids. Therefore, dasatinib could be an alternative treatment for patients with keloids.
ISSN:0001-5555
1651-2057
DOI:10.2340/actadv.v103.4475