Epidermolysis Bullosa Simplex
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Author(s):  
Mathilde C.S.C. Vermeer ◽  
Herman H.W. Sillje ◽  
Hendri H. Pas ◽  
Daniela Andrei ◽  
Peter van der Meer ◽  
...  

2022 ◽  
Vol 23 (1) ◽  
pp. 87
Author(s):  
Kakali Roy ◽  
Mizanul Haque ◽  
Bidisha Roy ◽  
Birendranath Roy

Author(s):  
Jen‐Ping Chao ◽  
Jing‐Yi Lin ◽  
Cheng‐Ying Chiang ◽  
Tyng‐Shiuan Hsieh ◽  
Sung‐Jan Lin ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Fuying Chen ◽  
Lei Yao ◽  
Xue Zhang ◽  
Yan Gu ◽  
Hong Yu ◽  
...  

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.


2021 ◽  
Vol 22 (22) ◽  
pp. 12446
Author(s):  
Nadezhda A. Evtushenko ◽  
Arkadii K. Beilin ◽  
Anastasiya V. Kosykh ◽  
Ekaterina A. Vorotelyak ◽  
Nadya G. Gurskaya

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.


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