Transcriptome network analysis of inflammation and fibrosis in keloids

作者全名：Mao, Jiayi; Chen, Lu; Qian, Shutong; Wang, Yuhuan; Zhao, Binfan; Zhao, Qiuyu; Lu, Bolun; Mao, Xiyuan; Zhai, Peisong; Zhang, Yuguang; Zhang, Liucheng; Sun, Xiaoming

作者地址：[Mao, Jiayi; Qian, Shutong; Wang, Yuhuan; Zhao, Binfan; Zhao, Qiuyu; Lu, Bolun; Mao, Xiyuan; Zhang, Yuguang; Zhang, Liucheng; Sun, Xiaoming] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Sch Med, 639 Zhi Zao Ju Rd, Shanghai 200011, Peoples R China; [Chen, Lu] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Zhai, Peisong] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Oral & Maxillofacial Head & Neck Oncol, Shanghai, Peoples R China

通信作者：Zhang, YG; Zhang, LC; Sun, XM (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Sch Med, 639 Zhi Zao Ju Rd, Shanghai 200011, Peoples R China.

来源：JOURNAL OF DERMATOLOGICAL SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001205642100001

JCR分区：Q1

影响因子：3.8

年份：2024

卷号：113

期号：2

开始页：62

结束页：73

文献类型：Article

关键词：Keloid; Biological information analysis; Single cell sequencing; MicroRNA sequencing; Transcriptome sequencing

摘要：Background: Keloid (KL) is a common benign skin tumor. KL is typically characterized by significant fibrosis and an intensive inflammatory response. Therefore, a comprehensive understanding of the interactions between cellular inflammation and fibrotic cells is essential to elucidate the mechanisms driving the progression of KL and to develop therapeutics. Objective: Investigate the transcriptome landscape of inflammation and fibrosis in keloid scars. Methods: In this paper, we performed transcriptome sequencing and microRNA (miRNA) sequencing on unselected live cells from six human keloid tissues and normal skin tissues to elucidate a comprehensive transcriptome landscape. In addition, we used single-cell RNA sequencing (scRNA-seq) analysis to analyze intercellular communication networks and enrich fibroblast populations in two additional keloid and normal skin samples to study fibroblast diversity. Results: By RNA sequencing and a miRNA-mRNA-PPI network analysis, we identified miR-615-5p and miR122b-3p as possible miRNAs associated with keloids, as they differed most significantly in keloids. Similarly, COL3A1, COL1A2, THBS2, TNC, IGTA, THBS4, TGFB3 as genes with significant differences in keloid may be associated with keloid development. Using single-cell RNA sequencing data from 24,086 cells collected from normal or keloid, we report reconstructed intercellular signaling network analysis and aggregation to modules associated with specific cell subpopulations at the cellular level for keloid alterations. Conclusions: Our multitranscriptomic dataset delineates inflammatory and fibro heterogeneity of human keloids, underlining the importance of intercellular crosstalk between inflammatory cells and fibro cells and revealing potential therapeutic targets. (c) 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

基金机构：National Natural Science Foundation of China [82002053, 32000937, 82202467, 82202456]; Shanghai "Rising Stars of Medical Talents" Youth Development Program, Shanghai Clinical Research Center of Plastic and Reconstructive Surgery; Science and Technology Commission of Shanghai Municipality [22MC1940300]; Shanghai Municipal Health Commission [20204Y0354]; Shanghai Science and Technology Development Funds [22YF1421400]

基金资助正文：This research was supported by the National Natural Science Foundation of China (82002053, 32000937, 82202467, 82202456) , Shanghai "Rising Stars of Medical Talents" Youth Development Program, Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by Science and Technology Commission of Shanghai Municipality (Grant No. 22MC1940300) , Shanghai Municipal Health Commission (20204Y0354) , Shanghai Science and Technology Development Funds (22YF1421400) .