Keloids are characterized by excessive extracellular collagen and exaggerated scarring. Large-volume lesions can be functionally debilitating, therapeutically intractable, and psychologically devastating. A key barrier to translational momentum for novel antikeloid agents is the lack of a faithful high-content screen. We devised, to our knowledge, a previously unreported phenotype-based assay that measures secreted collagen by keloidal fibroblasts in tissue hypoxic conditions (1% oxygen). Four keloidal fibroblasts and 1 normal dermal fibroblast line were exposed to 199 kinase inhibitors. Of 199 kinase inhibitors, 41 (21%) and 71 (36%) increased and decreased the (mean collagen inhibition normalized to viability) by more than 10%, respectively. The most collagen suppressive agents were CGP60474 ( = 0.36), KIN001-244 ( = 0.55), and RAF265 ( = 0.58). The top candidate, CGP60474, consistently abolished collagens I and VII production, exhibited minimal global toxicity, and induced a fivefold increase in phosphorylated extracellular signal-regulated kinase. This proof-of-concept high-content screen can identify drugs that appear to target critical keloidal pathophysiology-collagen secretion.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10831310 | PMC |
| http://dx.doi.org/10.1016/j.xjidi.2023.100248 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Orthogonal upconversion nanocarriers for combined photodynamic therapy and precisely triggered gene silencing in combating keloids.
J Control Release
January 2025
Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address:
Keloids are pathological scars characterized by excessive fibroblast proliferation, abnormal collagen deposition, and chronic inflammation, which often result in high recurrence rates and limited treatment success. Targeting BACH1 with gene therapy has shown promise in regulating fibroblast activity and reducing inflammation. However, effective delivery systems for targeted gene therapy in keloids remain a major challenge.
View Article and Find Full Text PDFEIF4A3 Enhances the Proliferation and Cell Cycle Progression of Keloid Fibroblasts by Inducing the hsa_circ_0002198 Expression.
Clin Cosmet Investig Dermatol
December 2024
Plastic Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Peoples Republic of China'.
Background: Recent evidence suggests a crucial biological role for Circular RNAs (circRNAs) in keloid diseases, yet the underlying mechanisms remain unclear. This study explored the biological effects and molecular mechanisms of hsa_circ_0002198 in keloid formation.
Methods: Real-time quantitative PCR (qRT-PCR) was employed to assess the expression of circ_0002198 in keloid tissues, normal skin tissues, keloid fibroblasts (KFs), and normal skin fibroblasts (NFs) from nine patients.
FoxC1 activates Notch3 signaling to promote the inflammatory phenotype of keloid fibroblasts and aggravates keloid.
Exp Cell Res
January 2025
Department of Plastic Surgery, The First Affiliated Hospital of Anhui Medical University, Anhui, 230032, China. Electronic address:
Keloids are disfiguring proliferative scars, and their pathological mechanisms are still unclear. We have previously established that FoxC1 plays a significant role in rheumatoid arthritis and osteoarthritis, but its molecular mechanisms in pathological scar formation remain elusive. In this study, we analyzed keloid tissue characteristics using HE staining and immunohistochemistry, revealing abnormal expression of FoxC1 and Notch3 in keloids.
View Article and Find Full Text PDFSingle cell transcriptomics reveals the cellular heterogeneity of keloids and the mechanism of their aggressiveness.
Commun Biol
December 2024
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Keloid is a dermatofibrotic disease known for its aggressive nature and characterized by pathological scarring, which often leads to disfigurement and frequent recurrences. Effective therapies for keloids are still limited, presumably due to the inadequate comprehension of their aggressive mechanisms. In our study, we examined the unique scenario where both keloid and non-aggressive pathological scar originate from the same patient, providing a rare opportunity to explore the aggressive mechanisms of keloids through single-cell RNA sequencing.
View Article and Find Full Text PDFExposure of Primary Human Skin Fibroblasts to Carbon Dioxide-Containing Solution Significantly Reduces TGF-β-Induced Myofibroblast Differentiation In Vitro.
Int J Mol Sci
December 2024
Department for Orthopedics and Trauma Surgery, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Dusseldorf, Germany.
Wound healing as a result of a skin injury involves a series of dynamic physiological processes, leading to wound closure, re-epithelialization, and the remodeling of the extracellular matrix (ECM). The primary scar formed by the new ECM never fully regains the original tissue's strength or flexibility. Moreover, in some cases, due to dysregulated fibroblast activity, proliferation, and differentiation, the normal scarring can be replaced by pathological fibrotic tissue, leading to hypertrophic scars or keloids.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!