Dataset Information

Multi-omics integrative analysis reveals the role of tumor necrosis factor superfamily member 4 in keloidal scarring.

ABSTRACT:

Objectives

To identify aberrantly expressed immune molecules in keloids and to explore their possible biologic significance.

Methods

Immune molecules with abnormal expression were identified based on immune gene sequencing of keloids, microarray datasets and high-throughput sequencing datasets and methylation microarray datasets from the Gene Expression Omnibus (GEO) database, and real-time quantitative PCR analysis.

Results

Upregulation of tumor necrosis factor superfamily member 4 (TNFSF4) in keloids was identified. Enrichment analysis found that high TNFSF4 expression was associated with immune processes, such as regulation of neutrophil chemotaxis, dendritic cell chemotaxis, and antigen processing and presentation. Single-cell RNA sequencing (scRNA) results suggested that TNFSF4 was upregulated in mesenchymal fibroblasts, which are the critical cells in skin fibrosis. This high expression of TNFSF4 enhanced cell-to-cell interactions in fibrosis-related pathways, including the fibronectin 1 (FN1) and collagen pathways. Mesenchymal fibroblasts expressing TNFSF4 significantly upregulated gene expression in extracellular matrix organization and wound healing processes.

Conclusions

Our study revealed upregulation of the immune molecule TNFSF4 in keloids at the multi-omics level and its effects on intercellular crosstalk and transcriptional profiles of mesenchymal fibroblasts. Investigation of TNFSF4 as an immune checkpoint molecule may represent a new direction for keloid treatment research.

SUBMITTER: Xia Y

PROVIDER: S-EPMC10086931 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Multi-omics integrative analysis reveals the role of tumor necrosis factor superfamily member 4 in keloidal scarring.

Xia Yijun Y Wang Youbin Y Hao Yan Y Shan Mengjie M Liu Hao H Liang Zhengyun Z

American journal of translational research 20230315 3

<h4>Objectives</h4>To identify aberrantly expressed immune molecules in keloids and to explore their possible biologic significance.<h4>Methods</h4>Immune molecules with abnormal expression were identified based on immune gene sequencing of keloids, microarray datasets and high-throughput sequencing datasets and methylation microarray datasets from the Gene Expression Omnibus (GEO) database, and real-time quantitative PCR analysis.<h4>Results</h4>Upregulation of tumor necrosis factor superfamily ...[more]

PMID: 37056826

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Project description:UnlabelledThe airway epithelium is a semi-impermeable barrier whose disruption by growth factor reprogramming is associated with chronic airway diseases of humans. Transforming growth factor beta (TGFβ)-induced epithelial mesenchymal transition (EMT) plays important roles in airway remodeling characteristic of idiopathic lung fibrosis, asthma and chronic obstructive pulmonary disease (COPD). Inflammation of the airways leads to airway injury and tumor necrosis factor alpha (TNFα) plays an important pro-inflammatory role. Little systematic information about the effects of EMT on TNFα signaling is available. Using an in vitro model of TGFβ-induced EMT in primary human small airway epithelial cells (hSAECs), we applied quantitative proteomics and phosphoprotein profiling to understand the molecular mechanism of EMT and the impact of EMT on innate inflammatory responses. We quantified 7925 proteins and 1348 phosphorylation sites by stable isotope labeling with iTRAQ technology. We found that cellular response to TNFα is cell state dependent and the relative TNFα response in mesenchymal state is highly compressed. Combined bioinformatics analyses of proteome and phosphoproteome indicate that the EMT state is associated with reprogramming of kinome, signaling cascade of upstream transcription regulators, phosphor-networks, and NF-κB dependent cell signaling.Biological significanceEpithelial mesenchymal transition and inflammation have important implications for clinical and physiologic manifestations of chronic airway diseases such as severe asthma, COPD, and lung fibrosis. Little systematic information on the interplay between EMT and innate inflammation is available. This study combined quantitative proteomics and phosphorproteomics approach to obtain systems-level insight into the upstream transcription regulators involved in the TGFβ-induced EMT in primary human small airway epithelial cells and to elucidate how EMT impacts on the TNFα signaling pathways. The proteomics and phosphoproteomics analysis indicates that many signaling pathways involved in TGFβ-induced EMT and EMT has profound reprogramming effects on innate inflammation response.

Dataset Information

Multi-omics integrative analysis reveals the role of tumor necrosis factor superfamily member 4 in keloidal scarring.

Objectives

Methods

Results

Conclusions

Publications

Multi-omics integrative analysis reveals the role of tumor necrosis factor superfamily member 4 in keloidal scarring.

Similar Datasets

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