Identification of potential hub genes associated with atopic dermatitis-like recombinant human epidermal model using integrated transcriptomic and proteomic analysis

Atopic dermatitis (AD) is a severe inflammatory skin disorder, characterized by elevated levels of proinflammatory cytokines that fuel a vicious cycle of inflammation. While inflammatory recombinant human epidermal (RHE) models relevant to AD have been established, comprehensive understanding remai...

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Main Authors: Wu Qiao, Tong Xie, Jing Lu, Tinghan Jia, Ken Kaku
Format: Article
Language:English
Published: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2024-01-01
Series:Biomolecules & Biomedicine
Subjects:
Online Access:https://www.bjbms.org/ojs/index.php/bjbms/article/view/9439
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author Wu Qiao
Tong Xie
Jing Lu
Tinghan Jia
Ken Kaku
author_facet Wu Qiao
Tong Xie
Jing Lu
Tinghan Jia
Ken Kaku
author_sort Wu Qiao
collection DOAJ
description Atopic dermatitis (AD) is a severe inflammatory skin disorder, characterized by elevated levels of proinflammatory cytokines that fuel a vicious cycle of inflammation. While inflammatory recombinant human epidermal (RHE) models relevant to AD have been established, comprehensive understanding remains limited. To illuminate changes and identify potential hub genes involved in AD-related inflammation, RHE models, stimulated by an inflammatory cocktail including polyinosinic-polycytidylic acid, tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4) and interleukin 13 (IL-13), were constructed and examined using tandem mass tags-proteomic coupled with RNA-seq transcriptomic analyses. Principal component analysis (PCA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment were employed for the analysis of related genes and proteins. Protein-protein interaction networks helped identify hub genes, which were further confirmed by qPCR and western blot. We observed high expression of thymic stromal lymphopoietin in the inflammatory RHE. Our study identified 2369 differentially expressed genes and 880 differentially expressed proteins in the cocktail-induced group versus the normal control group. A total of 248 overlapping symbols were enriched in various biological processes and signaling pathways, including cornification envelope, cell-cell junction, calcium ion binding, extracellular matrix receptor, terpenoid backbone biosynthesis, and peroxisome proliferator-activated receptors signaling pathway, among others. Among the 248 overlapping symbols, CytoHubba identified 10 hub molecules, namely signal transducer and activator of transcription 3 (STAT3), integrin subunit beta 1 (ITGB1), filaggrin (FLG), involucrin (IVL), DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 (DDX58), small proline rich protein 1B (SPRR1B), interferon induced with helicase C domain 1 (IFIH1), desmoglein 1 (DSG1), collagen type XVII alpha 1 chain (COL17A1), and integrin subunit alpha 6 (ITGA6), based on the degree. These integrated results offer valuable insights into the molecular mechanisms of AD and present potential tools for screening cosmetic formulations intended for the treatment of AD.
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spelling doaj.art-cb2d824296c449d58cfe6b35971f93692024-03-15T13:21:11ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2024-01-0124110.17305/bb.2023.9439Identification of potential hub genes associated with atopic dermatitis-like recombinant human epidermal model using integrated transcriptomic and proteomic analysisWu Qiao0https://orcid.org/0000-0003-0782-4478Tong Xie1Jing Lu2Tinghan Jia3Ken Kaku4Pigeon Manufacturing Shanghai CO., LTD., Shanghai, ChinaPigeon Manufacturing Shanghai CO., LTD., Shanghai, ChinaPigeon Manufacturing Shanghai CO., LTD., Shanghai, ChinaPigeon Manufacturing Shanghai CO., LTD., Shanghai, ChinaPigeon Manufacturing Shanghai CO., LTD., Shanghai, China Atopic dermatitis (AD) is a severe inflammatory skin disorder, characterized by elevated levels of proinflammatory cytokines that fuel a vicious cycle of inflammation. While inflammatory recombinant human epidermal (RHE) models relevant to AD have been established, comprehensive understanding remains limited. To illuminate changes and identify potential hub genes involved in AD-related inflammation, RHE models, stimulated by an inflammatory cocktail including polyinosinic-polycytidylic acid, tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4) and interleukin 13 (IL-13), were constructed and examined using tandem mass tags-proteomic coupled with RNA-seq transcriptomic analyses. Principal component analysis (PCA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment were employed for the analysis of related genes and proteins. Protein-protein interaction networks helped identify hub genes, which were further confirmed by qPCR and western blot. We observed high expression of thymic stromal lymphopoietin in the inflammatory RHE. Our study identified 2369 differentially expressed genes and 880 differentially expressed proteins in the cocktail-induced group versus the normal control group. A total of 248 overlapping symbols were enriched in various biological processes and signaling pathways, including cornification envelope, cell-cell junction, calcium ion binding, extracellular matrix receptor, terpenoid backbone biosynthesis, and peroxisome proliferator-activated receptors signaling pathway, among others. Among the 248 overlapping symbols, CytoHubba identified 10 hub molecules, namely signal transducer and activator of transcription 3 (STAT3), integrin subunit beta 1 (ITGB1), filaggrin (FLG), involucrin (IVL), DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 (DDX58), small proline rich protein 1B (SPRR1B), interferon induced with helicase C domain 1 (IFIH1), desmoglein 1 (DSG1), collagen type XVII alpha 1 chain (COL17A1), and integrin subunit alpha 6 (ITGA6), based on the degree. These integrated results offer valuable insights into the molecular mechanisms of AD and present potential tools for screening cosmetic formulations intended for the treatment of AD. https://www.bjbms.org/ojs/index.php/bjbms/article/view/9439Atopic dermatitistranscriptomicproteomicrecombinant human epidermalinflammatory
spellingShingle Wu Qiao
Tong Xie
Jing Lu
Tinghan Jia
Ken Kaku
Identification of potential hub genes associated with atopic dermatitis-like recombinant human epidermal model using integrated transcriptomic and proteomic analysis
Biomolecules & Biomedicine
Atopic dermatitis
transcriptomic
proteomic
recombinant human epidermal
inflammatory
title Identification of potential hub genes associated with atopic dermatitis-like recombinant human epidermal model using integrated transcriptomic and proteomic analysis
title_full Identification of potential hub genes associated with atopic dermatitis-like recombinant human epidermal model using integrated transcriptomic and proteomic analysis
title_fullStr Identification of potential hub genes associated with atopic dermatitis-like recombinant human epidermal model using integrated transcriptomic and proteomic analysis
title_full_unstemmed Identification of potential hub genes associated with atopic dermatitis-like recombinant human epidermal model using integrated transcriptomic and proteomic analysis
title_short Identification of potential hub genes associated with atopic dermatitis-like recombinant human epidermal model using integrated transcriptomic and proteomic analysis
title_sort identification of potential hub genes associated with atopic dermatitis like recombinant human epidermal model using integrated transcriptomic and proteomic analysis
topic Atopic dermatitis
transcriptomic
proteomic
recombinant human epidermal
inflammatory
url https://www.bjbms.org/ojs/index.php/bjbms/article/view/9439
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AT tongxie identificationofpotentialhubgenesassociatedwithatopicdermatitislikerecombinanthumanepidermalmodelusingintegratedtranscriptomicandproteomicanalysis
AT jinglu identificationofpotentialhubgenesassociatedwithatopicdermatitislikerecombinanthumanepidermalmodelusingintegratedtranscriptomicandproteomicanalysis
AT tinghanjia identificationofpotentialhubgenesassociatedwithatopicdermatitislikerecombinanthumanepidermalmodelusingintegratedtranscriptomicandproteomicanalysis
AT kenkaku identificationofpotentialhubgenesassociatedwithatopicdermatitislikerecombinanthumanepidermalmodelusingintegratedtranscriptomicandproteomicanalysis