Collagen I-discoidin domain receptor 1 signalling promotes inflammation development during keloid formation
作者:Yabing Hu, X. H. Xie, Huayu Huang, Longshan Li, Yixiao Xiong, Yuyang Zeng, Dan Li, Ying Xia, Yi Duan, Yongchu Huang, Yong Zhang, Xiaochao Zhang · 发表于:British Journal of Dermatology · 年份:2026 · DOI:10.1093/bjd/ljag105 · 被引用次数:3 · 研究领域:Dermatologic Treatments and Research、Wound Healing and Treatments、Hair Growth and Disorders
BACKGROUND: Keloid formation is a chronic inflammatory skin disease, characterized by abnormal fibroproliferative scars. There are no effective treatments. Many factors are involved in keloid formation, primarily a highly active inflammatory response, wound tension and hereditary susceptibility. Collagen signalling plays important roles in various diseases, including fibrotic diseases and tumours, but its function in keloid inflammation remains unknown. OBJECTIVES: To study the roles and mechanisms of collagen signalling in inflammation development during keloid formation. METHODS: Normal and keloid keratinocytes along with fibroblasts were isolated from fresh normal skin and keloid tissues. Picrosirius red staining, Western blotting, quantitative polymerase chain reaction, co-immunoprecipitation, APEX2-mediated proximity biotinylation, enzyme-linked immunosorbent assay, immunohistochemistry and immunofluorescence were used to discover the roles of collagen I-discoidin domain receptor 1 (DDR1) signalling in the development of inflammation. Human keloid samples were subcutaneously transplanted onto nude mice to build a keloid xenograft model. The therapeutic potential of a DDR1 inhibitor (7rh) and an ADP-ribosylation factor 6 (ARF6) inhibitor (NAV-2729) was examined in keloid inflammation development. RESULTS: In keloid tissue, we found significant elevation of both phosphorylated nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). In...