Biomechanical Regulatory Factors and Therapeutic Targets in Keloid Fibrosis.
biomechanical factor
fibroblast
keloid fibrosis
matrix force
mechanotransduction
targeted therapy
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2022
2022
Historique:
received:
28
03
2022
accepted:
25
04
2022
entrez:
26
5
2022
pubmed:
27
5
2022
medline:
27
5
2022
Statut:
epublish
Résumé
Keloids are fibroproliferative skin disorder caused by abnormal healing of injured or irritated skin and are characterized by excessive extracellular matrix (ECM) synthesis and deposition, which results in excessive collagen disorders and calcinosis, increasing the remodeling and stiffness of keloid matrix. The pathogenesis of keloid is very complex, and may include changes in cell function, genetics, inflammation, and other factors. In this review, we aim to discuss the role of biomechanical factors in keloid formation. Mechanical stimulation can lead to excessive proliferation of wound fibroblasts, deposition of ECM, secretion of more pro-fibrosis factors, and continuous increase of keloid matrix stiffness. Matrix mechanics resulting from increased matrix stiffness further activates the fibrotic phenotype of keloid fibroblasts, thus forming a loop that continuously invades the surrounding normal tissue. In this process, mechanical force is one of the initial factors of keloid formation, and matrix mechanics leads to further keloid development. Next, we summarized the mechanotransduction pathways involved in the formation of keloids, such as TGF-β/Smad signaling pathway, integrin signaling pathway, YAP/TAZ signaling pathway, and calcium ion pathway. Finally, some potential biomechanics-based therapeutic concepts and strategies are described in detail. Taken together, these findings underscore the importance of biomechanical factors in the formation and progression of keloids and highlight their regulatory value. These findings may help facilitate the development of pharmacological interventions that can ultimately prevent and reduce keloid formation and progression.
Identifiants
pubmed: 35614943
doi: 10.3389/fphar.2022.906212
pii: 906212
pmc: PMC9124765
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
906212Informations de copyright
Copyright © 2022 Feng, Liu, Pan, Wu, Wang, Yang, Liu, Xu and Lei.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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