Epidermolysis bullosa simplex due to KRT5 mutations: mutation-related differences in cellular fragility and the protective effects of trimethylamine N-oxide in cultured primary keratinocytes

The British Journal of Dermatology
Jean Christopher ChamcheuHans Törmä

Abstract

Epidermolysis bullosa simplex (EBS) is a mechanobullous skin fragility disease characterized by cytolysis of basal keratinocytes and intraepidermal blistering often caused by mutations in keratin genes (KRT5 or KRT14). No remedies exist for these disorders presenting a need for development of novel therapies. To identify new genotype-phenotype relationships in vivo and in cultured primary EBS keratinocytes in vitro, and to study the cytoskeletal stabilizing effects of trimethylamine N-oxide (TMAO) in heat-stressed EBS cells. Genomic DNA and cDNA samples from three Swedish patients with EBS were analysed for keratin mutations. Primary EBS keratinocyte cultures were established, heat stressed with and without added TMAO, followed by evaluation of cellular fragility. In addition to the previously reported KRT5 mutation (V186L) in one patient, two patients were found to have a novel I183M and recurrent E475G replacements in KRT5. Cultured EBS keratinocytes did not exhibit keratin aggregates or cell loss, except in the patient with the p.I183M mutation who showed 3% aggregates and 2% cell loss. Upon transient heat stress the number of aggregate-containing cells increased to 21%, 27% and 13%, respectively, in the p.I183M, p.E475G and...Continue Reading

References

Jan 1, 1972·International Journal of Peptide and Protein Research·S Y Gerlsma, E R Stuur
Jul 1, 1983·Journal of Biochemistry·K Gekko, S Koga
Dec 22, 1999·Biochemical Pharmacology·M G Santoro
Oct 12, 2002·Journal of Cell Science·Mariella D'AlessandroE Birgitte Lane
Nov 9, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Hans TörmäMagnus Lindberg
Aug 3, 2006·The British Journal of Dermatology·K YasukawaH Shimizu
May 29, 2007·Experimental Cell Research·Jouni UittoJohn A McGrath
Aug 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michelle L KernsPierre A Coulombe
Aug 16, 2008·The Journal of Investigative Dermatology·Annamária Glász-BónaSarolta Kárpáti
Jul 10, 2009·The Journal of Clinical Investigation·Pierre A CoulombeElaine Fuchs

❮ Previous
Next ❯

Citations

May 13, 2014·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Yoshiyuki Suzuki
Sep 7, 2011·The Journal of Cell Biology·Reinhard WindofferRudolf E Leube
Jan 27, 2012·The Journal of Investigative Dermatology·Pierre A Coulombe, Chang-Hun Lee
Jul 27, 2012·The Journal of Investigative Dermatology·Gilly Padalon-BrauchJacob Mashiah
Aug 26, 2011·Bioarchitecture·Rudolf E LeubeReinhard Windoffer
Oct 27, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Catherine A O'NeillRalf Paus
Jan 14, 2018·International Journal of Dermatology·Kiyofumi Yamanishi
Dec 24, 2010·Archives of Biochemistry and Biophysics·Jean Christopher ChamcheuHasan Mukhtar

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.