{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:27:36Z","timestamp":1791919656107,"version":"4.3.4"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Epidermolysis bullosa simplex (EBS) is a blistering dermatosis that is mostly caused by dominant mutations in <jats:italic>KRT5<\/jats:italic> and <jats:italic>KRT14<\/jats:italic>. In this study, we investigated one patient with localized recessive EBS caused by novel homozygous c.1474T &amp;gt; C mutations in <jats:italic>KRT5<\/jats:italic>. 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 <jats:italic>KRT5<\/jats:italic> mutation. Inhibition of EGFR phosphorylation upregulated DSG1 levels in an <jats:italic>in vitro<\/jats:italic> model. Collectively, our findings suggest that this mutation leads to localized recessive EBS and that keratin 5 is involved in maintaining DSG1 <jats:italic>via<\/jats:italic> activating MAPK signaling.<\/jats:p>","DOI":"10.3389\/fgene.2021.736610","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T13:25:40Z","timestamp":1638365140000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Damaged Keratin Filament Network Caused by KRT5 Mutations in Localized Recessive Epidermolysis Bullosa Simplex"],"prefix":"10.3389","volume":"12","author":[{"given":"Fuying","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.jdermsci.2008.11.003","article-title":"Characterization of Immortalized Human Epidermolysis Bullosa Simplex (KRT5) Cell Lines: Trimethylamine N-Oxide Protects the Keratin Cytoskeleton against Disruptive Stress Condition","volume":"53","author":"Chamcheu","year":"2009","journal-title":"J. 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