Deciphering the single-cell transcriptome network in keloids with intra-lesional injection of triamcinolone acetonide combined with 5-fluorouracil
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Published:2023-05-19
Issue:
Volume:14
Page:
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ISSN:1664-3224
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Container-title:Frontiers in Immunology
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language:
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Short-container-title:Front. Immunol.
Author:
Xia Yijun,Wang Youbin,Hao Yan,Shan Mengjie,Liu Hao,Liang Zhengyun,Kuang Xinwen
Abstract
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.
Funder
National Natural Science Foundation of China
Beijing Municipal Science and Technology Commission
Publisher
Frontiers Media SA
Subject
Immunology,Immunology and Allergy