Single-cell RNA sequencing analysis reveals the role of TXNDC5 in keloid formation.

IF 2.5 4区医学 Q2 PATHOLOGY Cytojournal Pub Date : 2024-10-31 eCollection Date: 2024-01-01 DOI:10.25259/Cytojournal_58_2024

Zhikun Liu, Lining Xian, Jianmin Li, Shudan Zheng, Hongju Xie

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Abstract

Objective: Thioredoxin domain-containing protein 5 (TXNDC5) is associated with fibrosis in a variety of organs, but its mechanism of action in keloid is unclear. In this study, we aimed to investigate the mechanism of TXNDC5 in keloid.

Material and methods: Single-cell RNA sequencing data of keloid and normal scar samples obtained from public databases were normalized and clustered using the Seurat package. Pathway enrich analysis was conducted using biological process enrichment analysis and Gene Set Enrichment Analysis (GSEA). In addition, TXNDC5 expression and its effects on migration and invasion of keloid fibroblasts (KFs) were validated based on cell function experiments.

Results: A total of five cell types were obtained. The KF clusters were further clustered into two fibroblast subtypes (Fibroblast cells 1 and Fibroblast cells 2). Biological process enrichment analysis showed that transforming growth factor beta (TGF-β) signaling pathway was enriched in the two fibroblast subtypes. GSEA analysis demonstrated that genes in TGF-β signaling pathway were mainly enriched in Fibroblast cells 1, and that genes involved in cell proliferation, migration, and the TGF-β signaling pathway were all high-expressed in fibroblast cells 1. TXNDC5 was positively correlated with fibroblast proliferation, migration and TGF-β signaling pathway, and AUCell score. The cellular experiment confirmed that the messenger RNA and protein levels of TXNDC5 and TGF-β1 were high-expressed in KFs cells (P<0.001), and that knockdown of TXNDC5 downregulated TGF-β1 expression and inhibited migration and invasion of KFs (P<0.0001).

Conclusion: Our study indicated that TGF-β signaling pathway was enriched in fibroblast cells, and TXNDC5 was positively correlated with proliferation, migration, and TGF-β signaling pathway. Cellular experiment demonstrated that knocking down TXNDC5 downregulated TGF-β1 expression, and suppressed migration and invasion of KFs. The current discoveries provided a new therapeutic strategy for the treatment of keloid.

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单细胞 RNA 测序分析揭示了 TXNDC5 在瘢痕疙瘩形成过程中的作用。

目的：含硫氧还蛋白结构域蛋白5（TXNDC5）与多种器官的纤维化有关，但其在瘢痕疙瘩中的作用机制尚不清楚。本研究旨在探讨TXNDC5在瘢痕疙瘩中的作用机制：使用Seurat软件包对从公共数据库获得的瘢痕疙瘩和正常瘢痕样本的单细胞RNA测序数据进行归一化和聚类。利用生物过程富集分析和基因组富集分析（Gene Set Enrichment Analysis，GSEA）进行通路富集分析。此外，还根据细胞功能实验验证了TXNDC5的表达及其对瘢痕疙瘩成纤维细胞（KFs）迁移和侵袭的影响：结果：共获得了五种细胞类型。结果：共获得了五种细胞类型，并进一步将 KF 聚类为两种成纤维细胞亚型（成纤维细胞 1 和成纤维细胞 2）。生物过程富集分析表明，两种成纤维细胞亚型中都富集了转化生长因子β（TGF-β）信号通路。GSEA分析表明，TGF-β信号通路中的基因主要在成纤维细胞1中富集，参与细胞增殖、迁移和TGF-β信号通路的基因在成纤维细胞1中均高表达。TXNDC5与成纤维细胞的增殖、迁移和TGF-β信号通路以及AUCell评分呈正相关。细胞实验证实，TXNDC5 和 TGF-β1 的信使 RNA 和蛋白水平在 KFs 细胞中高表达（PPConclusion：我们的研究表明，成纤维细胞中富含TGF-β信号通路，TXNDC5与细胞增殖、迁移和TGF-β信号通路呈正相关。细胞实验表明，敲除TXNDC5可降低TGF-β1的表达，抑制KFs的迁移和侵袭。目前的发现为治疗瘢痕疙瘩提供了一种新的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytojournal PATHOLOGY-

CiteScore

2.20

自引率

42.10%

发文量

审稿时长

>12 weeks

期刊介绍： The CytoJournal is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Diagnostic Cytopathology including Molecular aspects. The journal is owned by the Cytopathology Foundation and published by the Scientific Scholar.