Multitranscriptome analysis reveals stromal cells in the papillary dermis to promote angiogenesis in psoriasis vulgaris

作者：Bo Zhang, Junpu Mei, Qijun Liao, Shan Zhou, He Huang, Hui Liu, Xiaoli Xu, Yafen Yu, Chao Wu, Wenjun Wang, Weining Hu, Tingting Zhu, Yin Zhang, Mengyun Chen, Caihong Zhu, Mengjun Yu, Jinping Gao, Xianfa Tang, Xiawei Liu, Ze Guo, Xiaodong Zheng, Zhuang Wen, Gang Chen, Lili Tang, Xiaoyan Ding, Hui Cheng, Yang Li, Hongyan Wang, Hui Li, Yangrui Zhang, Xing Fan, Rouxi Chen, Zherou Rong, Ping Liu, Shengxiu Liu, Zhen Yue, Peiguang Wang, Zhiming Cai, Min Gao, Zaixing Wang, Xiaodong Fang, Fusheng Zhou, Huayang Tang · 发表于：British Journal of Dermatology · 年份：2024 · DOI：10.1093/bjd/ljae459 · 被引用次数：9 · 研究领域：Psoriasis: Treatment and Pathogenesis、Skin Protection and Aging、Dermatology and Skin Diseases

BACKGROUND: The pathogenesis of psoriasis is incompletely understood. Growing evidence suggests the involvement of stromal cells in the inflammatory process. OBJECTIVES: To investigate the roles of stromal cells, including fibroblasts, vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), in the psoriatic inflammatory microenvironment, and the possible underlying mechanisms involved. METHODS: We used a combination of single-cell, spatial transcriptome and bulk RNA sequencing of lesional and nonlesional skin samples from patients with psoriasis vulgaris (PV) and healthy skin samples from unaffected individuals. RESULTS: By analysing transcriptomes from 364 098 single cells, we uncovered WNT5A+ (Wnt-5a) fibroblasts, ITIH5+ (inter-α-trypsin inhibitor heavy chain 5) VECs and VCAN+ (versican) VSMCs, with significantly increased proportions of these cells in the papillary dermis of lesional psoriatic skin. We defined eight unique subclusters of fibroblasts in the skin and observed a shift of WIF1+ (Wnt inhibitory factor 1) fibroblasts toward WNT5A+ fibroblasts, with abnormal activation of the noncanonical Wnt signalling pathway and increased angiogenic and proinflammatory capabilities. VSMCs were able to undergo phenotypic transformation from a contractile to a synthetic phenotype during the development of psoriatic inflammation. ITIH5+ VECs and VCAN+ VSMCs were found to have an essential role in regulating angiogenesis and vascular remodelling in the patholog...