Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex

Epidermolysis bullosa simplex (EBS) is a blistering dermatosis that is mostly caused by dominant mutations in KRT5 and KRT14. In this study, we investigated one patient with localized recessive EBS caused by novel homozygous c.1474T > C mutations in KRT5. Biochemical experiments showed a muta...

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Autores principales:	Fuying Chen, Lei Yao, Xue Zhang, Yan Gu, Hong Yu, Zhirong Yao, Jia Zhang, Ming Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	recessive EBS KRT5 genodermatosis desmoglein 1 keratin Genetics QH426-470
Acceso en línea:	https://doaj.org/article/6aa47f5ddd1c4cd1a6ba11c62dc42b34
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spelling	oai:doaj.org-article:6aa47f5ddd1c4cd1a6ba11c62dc42b342021-12-01T13:25:30ZDamaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex1664-802110.3389/fgene.2021.736610https://doaj.org/article/6aa47f5ddd1c4cd1a6ba11c62dc42b342021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.736610/fullhttps://doaj.org/toc/1664-8021Epidermolysis bullosa simplex (EBS) is a blistering dermatosis that is mostly caused by dominant mutations in KRT5 and KRT14. In this study, we investigated one patient with localized recessive EBS caused by novel homozygous c.1474T > C mutations in KRT5. Biochemical experiments showed a mutation-induced alteration in the keratin 5 structure, intraepidermal blisters, and collapsed keratin intermediate filaments, but no quantitative change at the protein levels and interaction between keratin 5 and keratin 14. Moreover, we found that MAPK signaling was inhibited, while desmosomal protein desmoglein 1 (DSG1) was upregulated upon KRT5 mutation. Inhibition of EGFR phosphorylation upregulated DSG1 levels in an in vitro model. Collectively, our findings suggest that this mutation leads to localized recessive EBS and that keratin 5 is involved in maintaining DSG1 via activating MAPK signaling.Fuying ChenFuying ChenLei YaoLei YaoXue ZhangXue ZhangYan GuYan GuHong YuZhirong YaoZhirong YaoJia ZhangJia ZhangMing LiMing LiFrontiers Media S.A.articlerecessive EBSKRT5genodermatosisdesmoglein 1keratinGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	recessive EBS KRT5 genodermatosis desmoglein 1 keratin Genetics QH426-470
spellingShingle	recessive EBS KRT5 genodermatosis desmoglein 1 keratin Genetics QH426-470 Fuying Chen Fuying Chen Lei Yao Lei Yao Xue Zhang Xue Zhang Yan Gu Yan Gu Hong Yu Zhirong Yao Zhirong Yao Jia Zhang Jia Zhang Ming Li Ming Li Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex
description	Epidermolysis bullosa simplex (EBS) is a blistering dermatosis that is mostly caused by dominant mutations in KRT5 and KRT14. In this study, we investigated one patient with localized recessive EBS caused by novel homozygous c.1474T > C mutations in KRT5. Biochemical experiments showed a mutation-induced alteration in the keratin 5 structure, intraepidermal blisters, and collapsed keratin intermediate filaments, but no quantitative change at the protein levels and interaction between keratin 5 and keratin 14. Moreover, we found that MAPK signaling was inhibited, while desmosomal protein desmoglein 1 (DSG1) was upregulated upon KRT5 mutation. Inhibition of EGFR phosphorylation upregulated DSG1 levels in an in vitro model. Collectively, our findings suggest that this mutation leads to localized recessive EBS and that keratin 5 is involved in maintaining DSG1 via activating MAPK signaling.
format	article
author	Fuying Chen Fuying Chen Lei Yao Lei Yao Xue Zhang Xue Zhang Yan Gu Yan Gu Hong Yu Zhirong Yao Zhirong Yao Jia Zhang Jia Zhang Ming Li Ming Li
author_facet	Fuying Chen Fuying Chen Lei Yao Lei Yao Xue Zhang Xue Zhang Yan Gu Yan Gu Hong Yu Zhirong Yao Zhirong Yao Jia Zhang Jia Zhang Ming Li Ming Li
author_sort	Fuying Chen
title	Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex
title_short	Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex
title_full	Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex
title_fullStr	Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex
title_full_unstemmed	Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex
title_sort	damaged keratin filament network caused by krt5 mutations in localized recessive epidermolysis bullosa simplex
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6aa47f5ddd1c4cd1a6ba11c62dc42b34
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Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex

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