Analysis of gene expression profiles and protein-protein interaction networks in multiple tissues of systemic sclerosis

Elham Karimizadeh,Seyedehsaba Salehi,Farhad Gharibdoost,Mahdi Mahmoudi,Bahar Salamatian,Hassan Nikaein,Naser Elmi,Ali Sharifi-Zarchi

doi:10.1186/s12920-019-0632-2

Abstract

BackgroundSystemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The mechanisms underlying tissue pathology in SSc have not been entirely understood. This study intended to investigate the common and tissue-specific pathways involved in different tissues of SSc patients.MethodsAn integrative gene expression analysis of ten independent microarray datasets of three tissues was conducted to identify differentially expressed genes (DEGs). DEGs were mapped to the search tool for retrieval of interacting genes (STRING) to acquire protein–protein interaction (PPI) networks. Then, functional clusters in PPI networks were determined. Enrichr, a gene list enrichment analysis tool, was utilized for the functional enrichment of clusters.ResultsA total of 12, 2, and 4 functional clusters from 619, 52, and 119 DEGs were determined in the lung, peripheral blood mononuclear cell (PBMC), and skin tissues, respectively. Analysis revealed that the tumor necrosis factor (TNF) signaling pathway was enriched significantly in the three investigated tissues as a common pathway. In addition, clusters associated with inflammation and immunity were common in the three investigated tissues. However, clusters related to the fibrosis process were common in lung and skin tissues.ConclusionsAnalysis indicated that there were common pathological clusters that contributed to the pathogenesis of SSc in different tissues. Moreover, it seems that the common pathways in distinct tissues stem from a diverse set of genes.

Highlights

Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis
The exact pathogenesis of SSc remains unknown, but it seems that vascular abnormalities, inflammation, dysregulation of immune system, and extracellular matrix (ECM) deposition can lead to progressive connective tissue fibrosis
In the cluster L.1, the most significant biological processes and pathways were associated with immunity and inflammatory responses, including cytokine- and chemokine-mediated signaling pathways, cytokinecytokine receptor interaction, as well as JAK-STAT and tumor necrosis factor (TNF) signaling pathways

Summary

Introduction

Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The exact pathogenesis of SSc remains unknown, but it seems that vascular abnormalities, inflammation, dysregulation of immune system, and extracellular matrix (ECM) deposition can lead to progressive connective tissue fibrosis. Traditional researches have been performed in order to demonstrate the involvement of a particular gene or protein in SSc physiopathology [5, 6]. These studies generate invaluable data, they provide a small amount of evidence that is insufficient to clarify the complex interactions between multiple genes or proteins simultaneously. It is essential to utilize new approaches for realizing the alterations of different genes

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