Regulation of dermal fibroblasts by human neutrophil peptides

Abstract Human neutrophil peptides (HNPs) can induce cell proliferation and activation so their growth promoting activities may have potential clinical benefit. This study investigated the effects of HNPs on human dermal fibroblasts. Differential gene expression in HNP-treated cells and genes involv...

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Main Authors: Nattarika Niwetbowornchai, Thanawat Chaisirirat, Sira Sriswasdi, Supichcha Saithong, Grace Filbertine, Helen L. Wright, Steven W. Edwards, Sita Virakul, Direkrit Chiewchengchol
Format: Article
Language:English
Published: Nature Portfolio 2023-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-44889-8
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author Nattarika Niwetbowornchai
Thanawat Chaisirirat
Sira Sriswasdi
Supichcha Saithong
Grace Filbertine
Helen L. Wright
Steven W. Edwards
Sita Virakul
Direkrit Chiewchengchol
author_facet Nattarika Niwetbowornchai
Thanawat Chaisirirat
Sira Sriswasdi
Supichcha Saithong
Grace Filbertine
Helen L. Wright
Steven W. Edwards
Sita Virakul
Direkrit Chiewchengchol
author_sort Nattarika Niwetbowornchai
collection DOAJ
description Abstract Human neutrophil peptides (HNPs) can induce cell proliferation and activation so their growth promoting activities may have potential clinical benefit. This study investigated the effects of HNPs on human dermal fibroblasts. Differential gene expression in HNP-treated cells and genes involved in regulating intracellular pathways were explored. Dermal fibroblasts were isolated from healthy neonatal foreskin and treated with HNPs in 2D and 3D cell culture systems. The expression of cell proliferation (Ki-67) gene and cell activation (COL1A1) gene plus their proteins was measured. Differential gene expression was determined using RNA-seq, and upregulated and downregulated genes were mapped onto intracellular pathways by KEGG analysis and Gene Ontology databases. HNPs significantly increased cell proliferation without cytotoxicity whilst HNP1 enhanced expression of COL1A1 and type I collagen production in 2D cells and 3D spheroids. RNA-sequencing analysis showed gene clustering with clear separation between HNP1-treated and control groups. A heatmap of top 50 differentially expressed genes was consistent among HNP1-treated samples. Most upregulated genes were associated with cell proliferation and activation as mapped into intracellular pathways whilst most downregulated genes belonged to steroid/arachidonic acid metabolism and inflammatory signaling pathways. HNP1 increased cell proliferation and activation but reduced lipid metabolism and inflammation.
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spelling doaj.art-53b6a8e1c34147fa82e41ee32db253832023-11-20T09:29:03ZengNature PortfolioScientific Reports2045-23222023-10-0113111210.1038/s41598-023-44889-8Regulation of dermal fibroblasts by human neutrophil peptidesNattarika Niwetbowornchai0Thanawat Chaisirirat1Sira Sriswasdi2Supichcha Saithong3Grace Filbertine4Helen L. Wright5Steven W. Edwards6Sita Virakul7Direkrit Chiewchengchol8Center of Excellence in Translational Research in Inflammation and Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn UniversityCenter of Excellence in Computational Molecular Biology, Chulalongkorn UniversityCenter of Excellence in Computational Molecular Biology, Chulalongkorn UniversityCenter of Excellence in Translational Research in Inflammation and Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn UniversityCenter of Excellence in Translational Research in Inflammation and Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn UniversityInstitute of Life Course and Medical Sciences, University of LiverpoolInstitute of Infection, Veterinary and Ecological Sciences, University of LiverpoolCenter of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Immunology Unit, Chulalongkorn UniversityCenter of Excellence in Translational Research in Inflammation and Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn UniversityAbstract Human neutrophil peptides (HNPs) can induce cell proliferation and activation so their growth promoting activities may have potential clinical benefit. This study investigated the effects of HNPs on human dermal fibroblasts. Differential gene expression in HNP-treated cells and genes involved in regulating intracellular pathways were explored. Dermal fibroblasts were isolated from healthy neonatal foreskin and treated with HNPs in 2D and 3D cell culture systems. The expression of cell proliferation (Ki-67) gene and cell activation (COL1A1) gene plus their proteins was measured. Differential gene expression was determined using RNA-seq, and upregulated and downregulated genes were mapped onto intracellular pathways by KEGG analysis and Gene Ontology databases. HNPs significantly increased cell proliferation without cytotoxicity whilst HNP1 enhanced expression of COL1A1 and type I collagen production in 2D cells and 3D spheroids. RNA-sequencing analysis showed gene clustering with clear separation between HNP1-treated and control groups. A heatmap of top 50 differentially expressed genes was consistent among HNP1-treated samples. Most upregulated genes were associated with cell proliferation and activation as mapped into intracellular pathways whilst most downregulated genes belonged to steroid/arachidonic acid metabolism and inflammatory signaling pathways. HNP1 increased cell proliferation and activation but reduced lipid metabolism and inflammation.https://doi.org/10.1038/s41598-023-44889-8
spellingShingle Nattarika Niwetbowornchai
Thanawat Chaisirirat
Sira Sriswasdi
Supichcha Saithong
Grace Filbertine
Helen L. Wright
Steven W. Edwards
Sita Virakul
Direkrit Chiewchengchol
Regulation of dermal fibroblasts by human neutrophil peptides
Scientific Reports
title Regulation of dermal fibroblasts by human neutrophil peptides
title_full Regulation of dermal fibroblasts by human neutrophil peptides
title_fullStr Regulation of dermal fibroblasts by human neutrophil peptides
title_full_unstemmed Regulation of dermal fibroblasts by human neutrophil peptides
title_short Regulation of dermal fibroblasts by human neutrophil peptides
title_sort regulation of dermal fibroblasts by human neutrophil peptides
url https://doi.org/10.1038/s41598-023-44889-8
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