Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5

Pulmonary fibrosis is a serious disease characterized by extracellular matrix (ECM) component overproduction and remodeling. Insulin-like growth factor-binding protein 5 (IGFBP5) is a conserved member of the IGFBP family of proteins that is overexpressed in fibrotic tissues and promotes fibrosis. We...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xinh-Xinh Nguyen, Ludivine Renaud, Carol Feghali-Bostwick
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	insulin-like growth factor protein-5 (IGFBP5) transgenic model G-protein-coupled receptor (GPCR) neuroactive ligand receptor fibrosis transmembrane receptors Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c5a6d2ee7b824825a1564a8dc271b74b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c5a6d2ee7b824825a1564a8dc271b74b
record_format	dspace
spelling	oai:doaj.org-article:c5a6d2ee7b824825a1564a8dc271b74b2021-11-25T17:58:17ZIdentification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP510.3390/ijms2222126091422-00671661-6596https://doaj.org/article/c5a6d2ee7b824825a1564a8dc271b74b2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12609https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Pulmonary fibrosis is a serious disease characterized by extracellular matrix (ECM) component overproduction and remodeling. Insulin-like growth factor-binding protein 5 (IGFBP5) is a conserved member of the IGFBP family of proteins that is overexpressed in fibrotic tissues and promotes fibrosis. We used RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) between primary lung fibroblasts (pFBs) of homozygous (HOMO) transgenic mice expressing human IGFBP5 (hIGFBP5) and wild type mice (WT). The results of the differential expression analysis showed 2819 DEGs in hIGFBP5 pFBs. Functional enrichment analysis confirmed the pro-fibrotic character of IGFBP5 and revealed its impact on fundamental signaling pathways, including cytokine–cytokine receptor interaction, focal adhesion, AGE-RAGE signaling, calcium signaling, and neuroactive ligand-receptor interactions, to name a few. Noticeably, 7% of the DEGs in hIGFBP5-expressing pFBs are receptors and integrins. Furthermore, hub gene analysis revealed 12 hub genes including Fpr1, Bdkrb2, Mchr1, Nmur1, Cnr2, P2ry14, and Ptger3. Validation assays were performed to complement the RNAseq data. They confirmed significant differences in the levels of the corresponding proteins in cultured pFBs. Our study provides new insights into the molecular mechanism(s) of IGFBP5-associated pulmonary fibrosis through possible receptor interactions that drive fibrosis and tissue remodeling.Xinh-Xinh NguyenLudivine RenaudCarol Feghali-BostwickMDPI AGarticleinsulin-like growth factor protein-5 (IGFBP5)transgenic modelG-protein-coupled receptor (GPCR)neuroactive ligand receptorfibrosistransmembrane receptorsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12609, p 12609 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	insulin-like growth factor protein-5 (IGFBP5) transgenic model G-protein-coupled receptor (GPCR) neuroactive ligand receptor fibrosis transmembrane receptors Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	insulin-like growth factor protein-5 (IGFBP5) transgenic model G-protein-coupled receptor (GPCR) neuroactive ligand receptor fibrosis transmembrane receptors Biology (General) QH301-705.5 Chemistry QD1-999 Xinh-Xinh Nguyen Ludivine Renaud Carol Feghali-Bostwick Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5
description	Pulmonary fibrosis is a serious disease characterized by extracellular matrix (ECM) component overproduction and remodeling. Insulin-like growth factor-binding protein 5 (IGFBP5) is a conserved member of the IGFBP family of proteins that is overexpressed in fibrotic tissues and promotes fibrosis. We used RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) between primary lung fibroblasts (pFBs) of homozygous (HOMO) transgenic mice expressing human IGFBP5 (hIGFBP5) and wild type mice (WT). The results of the differential expression analysis showed 2819 DEGs in hIGFBP5 pFBs. Functional enrichment analysis confirmed the pro-fibrotic character of IGFBP5 and revealed its impact on fundamental signaling pathways, including cytokine–cytokine receptor interaction, focal adhesion, AGE-RAGE signaling, calcium signaling, and neuroactive ligand-receptor interactions, to name a few. Noticeably, 7% of the DEGs in hIGFBP5-expressing pFBs are receptors and integrins. Furthermore, hub gene analysis revealed 12 hub genes including Fpr1, Bdkrb2, Mchr1, Nmur1, Cnr2, P2ry14, and Ptger3. Validation assays were performed to complement the RNAseq data. They confirmed significant differences in the levels of the corresponding proteins in cultured pFBs. Our study provides new insights into the molecular mechanism(s) of IGFBP5-associated pulmonary fibrosis through possible receptor interactions that drive fibrosis and tissue remodeling.
format	article
author	Xinh-Xinh Nguyen Ludivine Renaud Carol Feghali-Bostwick
author_facet	Xinh-Xinh Nguyen Ludivine Renaud Carol Feghali-Bostwick
author_sort	Xinh-Xinh Nguyen
title	Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5
title_short	Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5
title_full	Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5
title_fullStr	Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5
title_full_unstemmed	Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5
title_sort	identification of impacted pathways and transcriptomic markers as potential mediators of pulmonary fibrosis in transgenic mice expressing human igfbp5
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c5a6d2ee7b824825a1564a8dc271b74b
work_keys_str_mv	AT xinhxinhnguyen identificationofimpactedpathwaysandtranscriptomicmarkersaspotentialmediatorsofpulmonaryfibrosisintransgenicmiceexpressinghumanigfbp5 AT ludivinerenaud identificationofimpactedpathwaysandtranscriptomicmarkersaspotentialmediatorsofpulmonaryfibrosisintransgenicmiceexpressinghumanigfbp5 AT carolfeghalibostwick identificationofimpactedpathwaysandtranscriptomicmarkersaspotentialmediatorsofpulmonaryfibrosisintransgenicmiceexpressinghumanigfbp5
_version_	1718411827885375488

Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5

Ejemplares similares