A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints. Though the current RA therapeutics such as disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biologics can halt the progression of the disease, none of these would eith...

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Main Authors: Venugopal Panga, Srivatsan Raghunathan
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC6013252?pdf=render
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author Venugopal Panga
Srivatsan Raghunathan
author_facet Venugopal Panga
Srivatsan Raghunathan
author_sort Venugopal Panga
collection DOAJ
description Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints. Though the current RA therapeutics such as disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biologics can halt the progression of the disease, none of these would either dramatically reduce or cure RA. So, the identification of potential therapeutic targets and new therapies for RA are active areas of research. Several studies have discovered the involvement of cytokines in the pathogenesis of this disease. These cytokines induce signal transduction pathways in RA synovial fibroblasts (RASF). These pathways share many signal transducers and their interacting proteins, resulting in the formation of a signaling network. In order to understand the involvement of this network in RA pathogenesis, it is essential to identify the key transducers and their interacting proteins that are part of this network. In this study, based on a detailed literature survey, we have identified a list of 12 cytokines that induce signal transduction pathways in RASF. For these cytokines, we have built a signaling network using the protein-protein interaction (PPI) data that was obtained from public repositories such as HPRD, BioGRID, MINT, IntAct and STRING. By combining the network centrality measures with the gene expression data from the RA related microarrays that are available in the open source Gene Expression Omnibus (GEO) database, we have identified 24 key proteins of this signaling network. Two of these 24 are already drug targets for RA, and of the remaining, 12 have direct PPI links to some of the current drug targets of RA. Therefore, these key proteins seem to be crucial in the pathogenesis of RA and hence might be treated as potential drug targets.
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spelling doaj.art-445617d93eb1499787781e6b3635bfce2022-12-21T19:07:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019953010.1371/journal.pone.0199530A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.Venugopal PangaSrivatsan RaghunathanRheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints. Though the current RA therapeutics such as disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biologics can halt the progression of the disease, none of these would either dramatically reduce or cure RA. So, the identification of potential therapeutic targets and new therapies for RA are active areas of research. Several studies have discovered the involvement of cytokines in the pathogenesis of this disease. These cytokines induce signal transduction pathways in RA synovial fibroblasts (RASF). These pathways share many signal transducers and their interacting proteins, resulting in the formation of a signaling network. In order to understand the involvement of this network in RA pathogenesis, it is essential to identify the key transducers and their interacting proteins that are part of this network. In this study, based on a detailed literature survey, we have identified a list of 12 cytokines that induce signal transduction pathways in RASF. For these cytokines, we have built a signaling network using the protein-protein interaction (PPI) data that was obtained from public repositories such as HPRD, BioGRID, MINT, IntAct and STRING. By combining the network centrality measures with the gene expression data from the RA related microarrays that are available in the open source Gene Expression Omnibus (GEO) database, we have identified 24 key proteins of this signaling network. Two of these 24 are already drug targets for RA, and of the remaining, 12 have direct PPI links to some of the current drug targets of RA. Therefore, these key proteins seem to be crucial in the pathogenesis of RA and hence might be treated as potential drug targets.http://europepmc.org/articles/PMC6013252?pdf=render
spellingShingle Venugopal Panga
Srivatsan Raghunathan
A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.
PLoS ONE
title A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.
title_full A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.
title_fullStr A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.
title_full_unstemmed A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.
title_short A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.
title_sort cytokine protein protein interaction network for identifying key molecules in rheumatoid arthritis
url http://europepmc.org/articles/PMC6013252?pdf=render
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