title: Correlation Network Analysis Reveals Relationships between MicroRNAs, Transcription Factor T-bet, and Deregulated Cytokine/Chemokine-Receptor Network in Pulmonary Sarcoidosis.
abstract: Sarcoidosis is an inflammatory granulomatous disease with unknown etiology driven by cytokines and chemokines. There is limited information regarding the regulation of cytokine/chemokine-receptor network in bronchoalveolar lavage (BAL) cells in pulmonary sarcoidosis, suggesting contribution of miRNAs and transcription factors. We therefore investigated gene expression of 25 inflammation-related miRNAs, 27 cytokines/chemokines/receptors, and a Th1-transcription factor T-bet in unseparated BAL cells obtained from 48 sarcoidosis patients and 14 control subjects using quantitative RT-PCR. We then examined both miRNA-mRNA expressions to enrich relevant relationships. This first study on miRNAs in sarcoid BAL cells detected deregulation of miR-146a, miR-150, miR-202, miR-204, and miR-222 expression comparing to controls. Subanalysis revealed higher number of miR-155, let-7c transcripts in progressing (n = 20) comparing to regressing (n = 28) disease as assessed by 2-year follow-up. Correlation network analysis revealed relationships between microRNAs, transcription factor T-bet, and deregulated cytokine/chemokine-receptor network in sarcoid BAL cells. Furthermore, T-bet showed more pronounced regulatory capability to sarcoidosis-associated cytokines/chemokines/receptors than miRNAs, which may function rather as "fine-tuners" of cytokine/chemokine expression. Our correlation network study implies contribution of both microRNAs and Th1-transcription factor T-bet to the regulation of cytokine/chemokine-receptor network in BAL cells in sarcoidosis. Functional studies are needed to confirm biological relevance of the obtained relationships.
authors.affiliation: Department of Immunology, Faculty of Medicine and Dentistry, Palacký University, 77515 Olomouc, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Dyskova
authors.affiliation: Department of Immunology, Faculty of Medicine and Dentistry, Palacký University, 77515 Olomouc, Czech Republic.
authors.forename: Regina
authors.initials: R
authors.lastname: Fillerova
authors.affiliation: IT4Innovations National Supercomputing Center and Faculty of Electrical Engineering and Computer Science, Department of Computer Science, VŠB-Technical University of Ostrava, 70800 Ostrava, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Novosad
authors.affiliation: IT4Innovations National Supercomputing Center and Faculty of Electrical Engineering and Computer Science, Department of Computer Science, VŠB-Technical University of Ostrava, 70800 Ostrava, Czech Republic.
authors.forename: Milos
authors.initials: M
authors.lastname: Kudelka
authors.affiliation: Department of Respiratory Diseases, Faculty of Medicine and Dentistry, Palacký University and Faculty Hospital, 77900 Olomouc, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Zurkova
authors.affiliation: IT4Innovations National Supercomputing Center and Faculty of Electrical Engineering and Computer Science, Department of Computer Science, VŠB-Technical University of Ostrava, 70800 Ostrava, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Gajdos
authors.affiliation: Department of Respiratory Diseases, Faculty of Medicine and Dentistry, Palacký University and Faculty Hospital, 77900 Olomouc, Czech Republic.
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Kolek
authors.affiliation: Department of Immunology, Faculty of Medicine and Dentistry, Palacký University, 77515 Olomouc, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Kriegova
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics*; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000502:physiology*; D000098815:T-bet Transcription Factor
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor