Deciphering the single-cell transcriptome network in keloids with intra-lesional injection of triamcinolone acetonide combined with 5-fluorouracil

Frontiers in Immunology

Immunology

Youbin Wang¹  Hao Liu¹  Yan Hao²  Yijun Xia²  Zhengyun Liang²  Mengjie Shan²  Xinwen Kuang² 

[1] Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China;Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China;

关键词: triamcinolone acetonide;    5-fluorouracil;    keloid;    scRNA;    transcriptome;   

DOI  :  10.3389/fimmu.2023.1106289

 received in 2022-11-25, accepted in 2023-05-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectivesKeloid is a highly aggressive fibrotic disease resulting from excessive extracellular matrix deposition after dermal injury. Intra-lesional injection of triamcinolone acetonide (TAC) in combination with 5-fluorouracil (5-FU) is a commonly used pharmacological regimen and long-term repeated injections can achieve sustained inhibition of keloid proliferation. However, the molecular mechanisms underlying the inhibitory effect on keloids remain insufficiently investigated.Methods and materialsThis study performed single-cell RNA sequencing analysis of keloids treated with TAC+5-FU injections, keloids, and skins to explore patterns of gene expression regulation and cellular reprogramming. ResultsThe results revealed that TAC+5-FU interrupted the differentiation trajectory of fibroblasts toward pro-fibrotic subtypes and induced keloid atrophy possibly by inhibiting the FGF signaling pathway in intercellular communication. It also stimulated partial fibroblasts to develop the potential for self-replication and multidirectional differentiation, which may be a possible cellular source of keloid recurrence. T cell dynamics demonstrated elevated expression of secretory globulin family members, which may be possible immunotherapeutic targets. Schwann cell populations achieved functional changes by increasing the proportion of apoptotic or senescence-associated cell populations and reducing cell clusters that promote epidermal development and fibroblast proliferation. ConclusionsOur findings elucidated the molecular and cellular reprogramming of keloids by intra-lesional injection of TAC+5-FU, which will provide new insights to understand the mechanism of action and therapeutic targets.

【 授权许可】

Unknown   
Copyright © 2023 Xia, Wang, Hao, Shan, Liu, Liang and Kuang