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  • Title: Expression of polydom in dermal neurofibroma and surrounding dermis in von Recklinghausen's disease.
    Author: Kamitani T, Murota H, Arase N, Wataya-Kaneda M, Sato-Nishiuchi R, Sekiguchi K, Okuzaki D, Motooka D, Katayama I.
    Journal: J Dermatol Sci; 2019 Nov; 96(2):73-80. PubMed ID: 31570272.
    Abstract:
    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: 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: Molecular, transcriptome and immunohistochemical analysis were performed to investigate the association between polydom expression and neurofibroma development. 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: Our results suggest that increased polydom expression in the dermis surrounding neurofibromas may promote dermal neurofibroma development by activating the TGF-β signaling pathway.
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