Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis
<i>Periodontitis</i> is a chronic inflammatory disease characterized by the progressive and irreversible destruction of the periodontium. Its aetiopathogenesis lies in the constant challenge of the dysbiotic biofilm, which triggers a deregulated immune response responsible for the diseas...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14835 |
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| author | Emiliano Vicencio Josefa Nuñez-Belmar Juan P. Cardenas Bastian I. Cortés Alberto J. M. Martin Vinicius Maracaja-Coutinho Adolfo Rojas Emilio A. Cafferata Luis González-Osuna Rolando Vernal Cristian Cortez |
| author_facet | Emiliano Vicencio Josefa Nuñez-Belmar Juan P. Cardenas Bastian I. Cortés Alberto J. M. Martin Vinicius Maracaja-Coutinho Adolfo Rojas Emilio A. Cafferata Luis González-Osuna Rolando Vernal Cristian Cortez |
| author_sort | Emiliano Vicencio |
| collection | DOAJ |
| description | <i>Periodontitis</i> is a chronic inflammatory disease characterized by the progressive and irreversible destruction of the periodontium. Its aetiopathogenesis lies in the constant challenge of the dysbiotic biofilm, which triggers a deregulated immune response responsible for the disease phenotype. Although the molecular mechanisms underlying periodontitis have been extensively studied, the regulatory mechanisms at the transcriptional level remain unclear. To generate transcriptomic data, we performed RNA shotgun sequencing of the oral mucosa of periodontitis-affected mice. Since genes are not expressed in isolation during pathological processes, we disclose here the complete repertoire of differentially expressed genes (DEG) and co-expressed modules to build Gene Regulatory Networks (GRNs) and identify the Master Transcriptional Regulators of periodontitis. The transcriptional changes revealed 366 protein-coding genes and 42 non-coding genes differentially expressed and enriched in the immune response. Furthermore, we found 13 co-expression modules with different representation degrees and gene expression levels. Our GRN comprises genes from 12 gene clusters, 166 nodes, of which 33 encode Transcription Factors, and 201 connections. Finally, using these strategies, 26 master regulators of periodontitis were identified. In conclusion, combining the transcriptomic analyses with the regulatory network construction represents a powerful and efficient strategy for identifying potential periodontitis-therapeutic targets. |
| first_indexed | 2024-03-10T21:42:20Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:42:20Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0024afa436fa4e10863501ac5fce2a4e2023-11-19T14:31:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124191483510.3390/ijms241914835Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis PathogenesisEmiliano Vicencio0Josefa Nuñez-Belmar1Juan P. Cardenas2Bastian I. Cortés3Alberto J. M. Martin4Vinicius Maracaja-Coutinho5Adolfo Rojas6Emilio A. Cafferata7Luis González-Osuna8Rolando Vernal9Cristian Cortez10Escuela de Tecnología Médica, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, ChileCentro de Genómica y Bioinformática, Facultad de Ciencias, Ingeniería y Tecnología, Universidad Mayor, Santiago 8580745, ChileCentro de Genómica y Bioinformática, Facultad de Ciencias, Ingeniería y Tecnología, Universidad Mayor, Santiago 8580745, ChileDepartamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileLaboratorio de Redes Biológicas, Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Fundación Ciencia & Vida, Santiago 7780272, ChileCentro de Modelamiento Molecular, Biofísica y Bioinformática, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380492, ChileCentro de Modelamiento Molecular, Biofísica y Bioinformática, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380492, ChileLaboratorio de Biología Periodontal, Facultad de Odontología, Universidad de Chile, Santiago 8380492, ChileLaboratorio de Biología Periodontal, Facultad de Odontología, Universidad de Chile, Santiago 8380492, ChileLaboratorio de Biología Periodontal, Facultad de Odontología, Universidad de Chile, Santiago 8380492, ChileEscuela de Tecnología Médica, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile<i>Periodontitis</i> is a chronic inflammatory disease characterized by the progressive and irreversible destruction of the periodontium. Its aetiopathogenesis lies in the constant challenge of the dysbiotic biofilm, which triggers a deregulated immune response responsible for the disease phenotype. Although the molecular mechanisms underlying periodontitis have been extensively studied, the regulatory mechanisms at the transcriptional level remain unclear. To generate transcriptomic data, we performed RNA shotgun sequencing of the oral mucosa of periodontitis-affected mice. Since genes are not expressed in isolation during pathological processes, we disclose here the complete repertoire of differentially expressed genes (DEG) and co-expressed modules to build Gene Regulatory Networks (GRNs) and identify the Master Transcriptional Regulators of periodontitis. The transcriptional changes revealed 366 protein-coding genes and 42 non-coding genes differentially expressed and enriched in the immune response. Furthermore, we found 13 co-expression modules with different representation degrees and gene expression levels. Our GRN comprises genes from 12 gene clusters, 166 nodes, of which 33 encode Transcription Factors, and 201 connections. Finally, using these strategies, 26 master regulators of periodontitis were identified. In conclusion, combining the transcriptomic analyses with the regulatory network construction represents a powerful and efficient strategy for identifying potential periodontitis-therapeutic targets.https://www.mdpi.com/1422-0067/24/19/14835periodontitischronic inflammationgene expressiontranscriptomegene regulatory networksmaster regulators transcription factors |
| spellingShingle | Emiliano Vicencio Josefa Nuñez-Belmar Juan P. Cardenas Bastian I. Cortés Alberto J. M. Martin Vinicius Maracaja-Coutinho Adolfo Rojas Emilio A. Cafferata Luis González-Osuna Rolando Vernal Cristian Cortez Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis International Journal of Molecular Sciences periodontitis chronic inflammation gene expression transcriptome gene regulatory networks master regulators transcription factors |
| title | Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis |
| title_full | Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis |
| title_fullStr | Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis |
| title_full_unstemmed | Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis |
| title_short | Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis |
| title_sort | transcriptional signatures and network based approaches identified master regulators transcription factors involved in experimental periodontitis pathogenesis |
| topic | periodontitis chronic inflammation gene expression transcriptome gene regulatory networks master regulators transcription factors |
| url | https://www.mdpi.com/1422-0067/24/19/14835 |
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