IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification

Lei Yu,1 Na Li,1 Jisheng Zhang,2 Yan Jiang1 1Department of Otorhinolaryngology, 2Key Laboratory of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, China Introduction: Epigenetic regulation has been shown to play an important role in the development of inflam...

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Autores principales:	Yu L, Li N, Zhang JS, Jiang Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	IL-13 H3K4me3 modification nasal epithelial cell differentiation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/06117dcc4baf4e35a5d9e22ecd151a61
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spelling	oai:doaj.org-article:06117dcc4baf4e35a5d9e22ecd151a612021-12-02T04:13:36ZIL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification1178-7031https://doaj.org/article/06117dcc4baf4e35a5d9e22ecd151a612018-01-01T00:00:00Zhttps://www.dovepress.com/il-13-regulates-human-nasal-epithelial-cell-differentiation-via-h3k4me-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Lei Yu,1 Na Li,1 Jisheng Zhang,2 Yan Jiang1 1Department of Otorhinolaryngology, 2Key Laboratory of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, China Introduction: Epigenetic regulation has been shown to play an important role in the development of inflammatory diseases, including chronic rhinosinusitis and nasal polyps. The latter are characterized by epithelial mis-differentiation and infiltration of inflammatory cytokines. H3K4me3 has been shown to be involved in regulating lineage commitment. However, the underlying mechanisms, especially in human nasal epithelial cells (HNEpC), remain underexplored. The objective of this study was to investigate the role of H3K4me3 in HNEpC differentiation treated with the Th2 cytokine IL-13. Patients and methods: The expression levels of mRNA and proteins were investigated using reverse transcription-polymerase chain reaction (RT-PCR) assays and Western blot in nasal polyp tissues and human nasal epithelial cells respectively. We measured these levels of H3K4me3, MLL1 and targeted genes compared with control subjects.Results: We demonstrate that expression of H3K4me3 and its methyltransferase MLL1 was significantly upregulated in IL-13-treated HNEpC. This elevation was also observed in nasal polyps. Expression of cilia-related transcription factors FOXJ1 and DNAI2 decreased, while goblet cell-derived genes CLCA1 and MUC5a increased upon IL-13 treatment. Mechanistically, knockdown of MLL1 restored expression of these four genes induced by IL-13. Conclusion: These findings suggest that H3K4me3 is a critical regulator in control of nasal epithelial cell differentiation. MLL1 may be a potential therapeutic target for nasal inflammatory diseases. Keywords: IL-13, H3K4me3 modification, nasal epithelial cell, differentiation Yu LLi NZhang JSJiang YDove Medical PressarticleIL-13H3K4me3 modificationnasal epithelial celldifferentiationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 10, Pp 181-188 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	IL-13 H3K4me3 modification nasal epithelial cell differentiation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	IL-13 H3K4me3 modification nasal epithelial cell differentiation Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Yu L Li N Zhang JS Jiang Y IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification
description	Lei Yu,1 Na Li,1 Jisheng Zhang,2 Yan Jiang1 1Department of Otorhinolaryngology, 2Key Laboratory of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, China Introduction: Epigenetic regulation has been shown to play an important role in the development of inflammatory diseases, including chronic rhinosinusitis and nasal polyps. The latter are characterized by epithelial mis-differentiation and infiltration of inflammatory cytokines. H3K4me3 has been shown to be involved in regulating lineage commitment. However, the underlying mechanisms, especially in human nasal epithelial cells (HNEpC), remain underexplored. The objective of this study was to investigate the role of H3K4me3 in HNEpC differentiation treated with the Th2 cytokine IL-13. Patients and methods: The expression levels of mRNA and proteins were investigated using reverse transcription-polymerase chain reaction (RT-PCR) assays and Western blot in nasal polyp tissues and human nasal epithelial cells respectively. We measured these levels of H3K4me3, MLL1 and targeted genes compared with control subjects.Results: We demonstrate that expression of H3K4me3 and its methyltransferase MLL1 was significantly upregulated in IL-13-treated HNEpC. This elevation was also observed in nasal polyps. Expression of cilia-related transcription factors FOXJ1 and DNAI2 decreased, while goblet cell-derived genes CLCA1 and MUC5a increased upon IL-13 treatment. Mechanistically, knockdown of MLL1 restored expression of these four genes induced by IL-13. Conclusion: These findings suggest that H3K4me3 is a critical regulator in control of nasal epithelial cell differentiation. MLL1 may be a potential therapeutic target for nasal inflammatory diseases. Keywords: IL-13, H3K4me3 modification, nasal epithelial cell, differentiation
format	article
author	Yu L Li N Zhang JS Jiang Y
author_facet	Yu L Li N Zhang JS Jiang Y
author_sort	Yu L
title	IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification
title_short	IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification
title_full	IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification
title_fullStr	IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification
title_full_unstemmed	IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification
title_sort	il-13 regulates human nasal epithelial cell differentiation via h3k4me3 modification
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/06117dcc4baf4e35a5d9e22ecd151a61
work_keys_str_mv	AT yul il13regulateshumannasalepithelialcelldifferentiationviah3k4me3modification AT lin il13regulateshumannasalepithelialcelldifferentiationviah3k4me3modification AT zhangjs il13regulateshumannasalepithelialcelldifferentiationviah3k4me3modification AT jiangy il13regulateshumannasalepithelialcelldifferentiationviah3k4me3modification
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IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification

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