Integrating Protein Interaction and Pathway Crosstalk Network Reveals a Promising Therapeutic Approach for Psoriasis Through Apoptosis Induction

Overview

Journal Sci Rep

Specialty Science

Date 2024 Sep 27

PMID 39333640

Authors

Masoumeh Farahani

Reza M Robati

Mostafa Rezaei-Tavirani

Fatemeh Fateminasab

Sergey Shityakov

Mohammad Rahmati Roodsari

Zahra Razzaghi

Mona Zamanian Azodi

Saviz Saghari

Affiliations

Soon will be listed here.

Abstract

Psoriasis is a complex inflammatory skin disease manifested by altered proliferation and differentiation of keratinocytes with dysfunctional apoptosis. This study aimed to identify regulatory factors and comprehend the underlying mechanisms of inefficient apoptosis to open up promising therapeutic approaches. Incorporating human protein interactions, apoptosis proteins, and physical relationships of psoriasis-apoptosis proteins helped us to generate a psoriasis-apoptosis interaction (SAI) network. Subsequently, topological and functional analyses of the SAI network revealed effective proteins, functional modules, hub motifs, dysregulated pathways and transcriptional gene regulatory factors. Network pharmacology, molecular docking and molecular dynamics simulation methods identified the potential drug-target interactions. RELA, MAPK1, MAPK3, MMP9, IL1B, AKT1 and STAT1 were revealed as effective proteins. The MAPK1-MAPK3-RELA motif was identified as a hub regulator in the crosstalk between 41 pathways. Among all pathways, "lipid and atherosclerosis" was found to be the predominant pathway. Acetylcysteine, arsenic-trioxide, β-elemene, bortezomib and curcumin were identified as potential drugs to inhibit pathway crosstalk. Experimental verifications were performed using the literature search, GSE13355 and GSE14905 microarray datasets. Drug-protein-pathway interactions associated with apoptosis were deciphered. These findings highlight the role of hub motif-mediated pathway-pathway crosstalk associated with apoptosis in the complexity of psoriasis and suggest crosstalk inhibition as an effective therapeutic approach.

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