Expression of polydom in dermal neurofibroma and surrounding dermis in von Recklinghausen's disease.
Adolescent
Adult
Aged
Base Sequence
Cell Adhesion
Cell Adhesion Molecules
/ metabolism
Dermis
/ metabolism
Female
Fibroblasts
/ metabolism
Gene Expression Regulation
Humans
Integrin beta Chains
/ metabolism
Male
Middle Aged
Neurofibroma
/ metabolism
Neurofibromatosis 1
/ metabolism
Proto-Oncogene Proteins c-sis
/ metabolism
RNA, Small Interfering
/ metabolism
Signal Transduction
Transforming Growth Factor beta
/ metabolism
Transforming Growth Factor beta1
/ metabolism
Young Adult
Neurofibroma
Platelet-derived growth factor B
Polydom
TGF-β
von Recklinghausen’s disease
Journal
Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
03
12
2018
revised:
06
08
2019
accepted:
12
09
2019
pubmed:
2
10
2019
medline:
23
6
2020
entrez:
2
10
2019
Statut:
ppublish
Résumé
Neurofibromas in von Recklinghausen's disease (vRD) can develop in the dermis. Therefore, we hypothesized that a dermal niche exists that promotes the development of these neurofibromas in subjects with vRD. The purpose of this study is to examine the function of polydom, known as a ligand for integrin, mediating cell adhesion, and expressed in mouse nerve tissue, in promotion of neurofibroma. Molecular, transcriptome and immunohistochemical analysis were performed to investigate the association between polydom expression and neurofibroma development. Polydom mRNA levels were significantly higher in neurofibroma tissue than in control tissue. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis of RNA purified from primary cultured dermal neurofibroma cells demonstrated significantly higher polydom mRNA expression in cells derived from the surrounding dermis of neurofibromas compared to those from normal human dermal fibroblasts. RNA sequencing was used to compare gene expression between cultured cells derived from dermal neurofibroma-surrounding tissue with or without polydom knockdown. Subsequent gene ontology assays revealed that expression of integrinβ8 (ITGB8), a factor that releases transforming growth factor-β (TGF-β) from pro-TGF-β, was downregulated following polydom knockdown, suggesting upregulation of polydom-mediated TGF-β production. Furthermore, we observed a strong association between polydom expression and the increase in platelet-derived growth factor B (PDGFB) expression in primary cultured cells from the surrounding dermis of neurofibromas exposed to TGF-β1. Our results suggest that increased polydom expression in the dermis surrounding neurofibromas may promote dermal neurofibroma development by activating the TGF-β signaling pathway.
Sections du résumé
BACKGROUND
BACKGROUND
Neurofibromas in von Recklinghausen's disease (vRD) can develop in the dermis. Therefore, we hypothesized that a dermal niche exists that promotes the development of these neurofibromas in subjects with vRD.
OBJECTIVE
OBJECTIVE
The purpose of this study is to examine the function of polydom, known as a ligand for integrin, mediating cell adhesion, and expressed in mouse nerve tissue, in promotion of neurofibroma.
METHODS
METHODS
Molecular, transcriptome and immunohistochemical analysis were performed to investigate the association between polydom expression and neurofibroma development.
RESULTS
RESULTS
Polydom mRNA levels were significantly higher in neurofibroma tissue than in control tissue. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis of RNA purified from primary cultured dermal neurofibroma cells demonstrated significantly higher polydom mRNA expression in cells derived from the surrounding dermis of neurofibromas compared to those from normal human dermal fibroblasts. RNA sequencing was used to compare gene expression between cultured cells derived from dermal neurofibroma-surrounding tissue with or without polydom knockdown. Subsequent gene ontology assays revealed that expression of integrinβ8 (ITGB8), a factor that releases transforming growth factor-β (TGF-β) from pro-TGF-β, was downregulated following polydom knockdown, suggesting upregulation of polydom-mediated TGF-β production. Furthermore, we observed a strong association between polydom expression and the increase in platelet-derived growth factor B (PDGFB) expression in primary cultured cells from the surrounding dermis of neurofibromas exposed to TGF-β1.
CONCLUSION
CONCLUSIONS
Our results suggest that increased polydom expression in the dermis surrounding neurofibromas may promote dermal neurofibroma development by activating the TGF-β signaling pathway.
Identifiants
pubmed: 31570272
pii: S0923-1811(19)30295-6
doi: 10.1016/j.jdermsci.2019.09.005
pii:
doi:
Substances chimiques
Cell Adhesion Molecules
0
Integrin beta Chains
0
Proto-Oncogene Proteins c-sis
0
RNA, Small Interfering
0
SVEP1 protein, human
0
TGFB1 protein, human
0
Transforming Growth Factor beta
0
Transforming Growth Factor beta1
0
integrin beta8
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
73-80Informations de copyright
Copyright © 2019. Published by Elsevier B.V.