Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex

Epidermolysis bullosa simplex (EBS) is a group of inherited keratinopathies that, in most cases, arise due to mutations in keratins and lead to intraepidermal ruptures. The cellular pathology of most EBS subtypes is associated with the fragility of the intermediate filament network, cytolysis of the...

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Autores principales:	Nadezhda A. Evtushenko, Arkadii K. Beilin, Anastasiya V. Kosykh, Ekaterina A. Vorotelyak, Nadya G. Gurskaya
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	epidermolysis bullosa simplex skin blistering epidermis keratinocyte basal layer Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/cefeec9340e64d1eb8def59d5d6fc35f
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spelling	oai:doaj.org-article:cefeec9340e64d1eb8def59d5d6fc35f2021-11-25T17:56:44ZKeratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex10.3390/ijms2222124461422-00671661-6596https://doaj.org/article/cefeec9340e64d1eb8def59d5d6fc35f2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12446https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Epidermolysis bullosa simplex (EBS) is a group of inherited keratinopathies that, in most cases, arise due to mutations in keratins and lead to intraepidermal ruptures. The cellular pathology of most EBS subtypes is associated with the fragility of the intermediate filament network, cytolysis of the basal layer of the epidermis, or attenuation of hemidesmosomal/desmosomal components. Mutations in keratins 5/14 or in other genes that encode associated proteins induce structural disarrangements of different strengths depending on their locations in the genes. Keratin aggregates display impaired dynamics of assembly and diminished solubility and appear to be the trigger for endoplasmic reticulum (ER) stress upon being phosphorylated by MAPKs. Global changes in cellular signaling mainly occur in cases of severe dominant EBS mutations. The spectrum of changes initiated by phosphorylation includes the inhibition of proteasome degradation, TNF-α signaling activation, deregulated proliferation, abnormal cell migration, and impaired adherence of keratinocytes. ER stress also leads to the release of proinflammatory danger-associated molecular pattern (DAMP) molecules, which enhance avalanche-like inflammation. Many instances of positive feedback in the course of cellular stress and the development of sterile inflammation led to systemic chronic inflammation in EBS. This highlights the role of keratin in the maintenance of epidermal and immune homeostasis.Nadezhda A. EvtushenkoArkadii K. BeilinAnastasiya V. KosykhEkaterina A. VorotelyakNadya G. GurskayaMDPI AGarticleepidermolysis bullosa simplexskinblisteringepidermiskeratinocytebasal layerBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12446, p 12446 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epidermolysis bullosa simplex skin blistering epidermis keratinocyte basal layer Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	epidermolysis bullosa simplex skin blistering epidermis keratinocyte basal layer Biology (General) QH301-705.5 Chemistry QD1-999 Nadezhda A. Evtushenko Arkadii K. Beilin Anastasiya V. Kosykh Ekaterina A. Vorotelyak Nadya G. Gurskaya Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex
description	Epidermolysis bullosa simplex (EBS) is a group of inherited keratinopathies that, in most cases, arise due to mutations in keratins and lead to intraepidermal ruptures. The cellular pathology of most EBS subtypes is associated with the fragility of the intermediate filament network, cytolysis of the basal layer of the epidermis, or attenuation of hemidesmosomal/desmosomal components. Mutations in keratins 5/14 or in other genes that encode associated proteins induce structural disarrangements of different strengths depending on their locations in the genes. Keratin aggregates display impaired dynamics of assembly and diminished solubility and appear to be the trigger for endoplasmic reticulum (ER) stress upon being phosphorylated by MAPKs. Global changes in cellular signaling mainly occur in cases of severe dominant EBS mutations. The spectrum of changes initiated by phosphorylation includes the inhibition of proteasome degradation, TNF-α signaling activation, deregulated proliferation, abnormal cell migration, and impaired adherence of keratinocytes. ER stress also leads to the release of proinflammatory danger-associated molecular pattern (DAMP) molecules, which enhance avalanche-like inflammation. Many instances of positive feedback in the course of cellular stress and the development of sterile inflammation led to systemic chronic inflammation in EBS. This highlights the role of keratin in the maintenance of epidermal and immune homeostasis.
format	article
author	Nadezhda A. Evtushenko Arkadii K. Beilin Anastasiya V. Kosykh Ekaterina A. Vorotelyak Nadya G. Gurskaya
author_facet	Nadezhda A. Evtushenko Arkadii K. Beilin Anastasiya V. Kosykh Ekaterina A. Vorotelyak Nadya G. Gurskaya
author_sort	Nadezhda A. Evtushenko
title	Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex
title_short	Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex
title_full	Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex
title_fullStr	Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex
title_full_unstemmed	Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex
title_sort	keratins as an inflammation trigger point in epidermolysis bullosa simplex
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cefeec9340e64d1eb8def59d5d6fc35f
work_keys_str_mv	AT nadezhdaaevtushenko keratinsasaninflammationtriggerpointinepidermolysisbullosasimplex AT arkadiikbeilin keratinsasaninflammationtriggerpointinepidermolysisbullosasimplex AT anastasiyavkosykh keratinsasaninflammationtriggerpointinepidermolysisbullosasimplex AT ekaterinaavorotelyak keratinsasaninflammationtriggerpointinepidermolysisbullosasimplex AT nadyaggurskaya keratinsasaninflammationtriggerpointinepidermolysisbullosasimplex
_version_	1718411831690657792

Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex

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