Identification and characterization of bone/cartilage-associated signatures in common fibrotic skin diseases.

Identification and characterization of bone/cartilage-associated signatures in common fibrotic skin diseases.
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DOI:
10.3389/fgene.2023.1121728
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发表时间:
2023
影响因子:
3.7
通讯作者:
Huang, Changzheng
Huang, Changzheng
中科院分区:
生物学3区
文献类型:
--
作者:
Wu, Ting;Jin, Yifan;Chen, Fangqi;Xuan, Xiuyun;Cao, Juanmei;Liang, Yan;Wang, Yuqing;Zhan, Jinshan;Zhao, Mengjie;Huang, Changzheng

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背景资料:纤维化皮肤病的特征在于细胞外基质(ECM)的过度积累和成纤维细胞的活化,导致全球医疗负担。然而,纤维化皮肤病的有效治疗仍然有限,其病理机制需要进一步研究。本研究旨在通过生物信息学分析,探讨瘢痕疙瘩和系统性硬化症(SSc)两种主要纤维化皮肤病的共同生物标志物和治疗靶点。 方法:从基因表达综合数据库(GEO)下载瘢痕疙瘩(GSE 92566)和SSc(GSE 95065)数据集。鉴定差异表达基因(DEG),然后使用基因本体(GO)和京都基因和基因组百科全书(KEGG)进行功能富集分析。然后,我们构建了一个蛋白质-蛋白质相互作用(PPI)网络的枢纽基因的识别。我们探索了在Metascape、GeneMANIA和TissueNexus平台上对枢纽基因进行进一步功能富集分析的可能性。使用NetworkAnalyst建立转录因子(TF)-hub基因和miRNA-hub基因网络。我们将GSE 90051和GSE 76855固定为外部验证数据集。使用Student t检验和受试者工作特征(ROC)曲线进行候选枢纽基因验证。通过定量实时PCR在体外评估Hub基因表达。 结果如下:从GSE 92566和GSE 95065数据集中共检索到157个重叠DEG(ODEG),并鉴定和验证了5个中心基因(COL 11 A1、COL 5A 2、ASPN、COL 10A 1和COMP)。功能研究表明,枢纽基因主要富集在骨/软骨相关和胶原相关的过程。FOXC 1和miR-335- 5 p被预测为转录和转录后水平的主要调控因子。 结论:COL 11 A1、COL 5A 2、ASPN、COL 10A 1和COMP可能有助于理解主要纤维化皮肤病的病理机制; FOXC 1和miR-355- 5 p可能在瘢痕疙瘩和SSc中构建调控网络。
Background: Fibrotic skin diseases are characterized by excessive accumulation of the extracellular matrix (ECM) and activation of fibroblasts, leading to a global healthcare burden. However, effective treatments of fibrotic skin diseases remain limited, and their pathological mechanisms require further investigation. This study aims to investigate the common biomarkers and therapeutic targets in two major fibrotic skin diseases, namely, keloid and systemic sclerosis (SSc), by bioinformatics analysis. Methods: The keloid (GSE92566) and SSc (GSE95065) datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by functional enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then constructed a protein–protein interaction (PPI) network for the identification of hub genes. We explored the possibility of further functional enrichment analysis of hub genes on the Metascape, GeneMANIA, and TissueNexus platforms. Transcription factor (TF)–hub gene and miRNA–hub gene networks were established using NetworkAnalyst. We fixed GSE90051 and GSE76855 as the external validation datasets. Student’s t-test and receiver operating characteristic (ROC) curve were used for candidate hub gene validation. Hub gene expression was assessed in vitro by quantitative real-time PCR. Results: A total of 157 overlapping DEGs (ODEGs) were retrieved from the GSE92566 and GSE95065 datasets, and five hub genes (COL11A1, COL5A2, ASPN, COL10A1, and COMP) were identified and validated. Functional studies revealed that hub genes were predominantly enriched in bone/cartilage-related and collagen-related processes. FOXC1 and miR-335-5p were predicted to be master regulators at both transcriptional and post‐transcriptional levels. Conclusion: COL11A1, COL5A2, ASPN, COL10A1, and COMP may help understand the pathological mechanism of the major fibrotic skin diseases; moreover, FOXC1 and miR-355-5p could build a regulatory network in keloid and SSc.
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发表时间: 2018-09-18
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