Cellular and Metabolic Basis for the Ichthyotic Phenotype in NIPAL4 (Ichthyin)-Deficient Canines
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10382596" target="_blank" >RIV/00216208:11160/18:10382596 - isvavai.cz</a>
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0002944017309732" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0002944017309732</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ajpath.2018.02.008" target="_blank" >10.1016/j.ajpath.2018.02.008</a>
Alternative languages
Result language
angličtina
Original language name
Cellular and Metabolic Basis for the Ichthyotic Phenotype in NIPAL4 (Ichthyin)-Deficient Canines
Original language description
Mutations in several Lipid synthetic enzymes that block fatty acid and ceramide production produce autosomal recessive congenital ichthyoses (ARCIs) and associated abnormalities in permeability barrier homeostasis. However, the basis for the phenotype in patients with NIPAL4 (ichthyin) mutations (among the most prevalent ARCIs) remains unknown. Barrier function was abnormal in an index patient and in canines with homozygous NIPAL4 mutations, attributable to extensive membrane stripping, likely from detergent effects of nonesterified free fatty acid. Cytotoxicity compromised not only lamellar body secretion but also formation of the corneocyte lipid envelope (CLE) and attenuation of the cornified envelope (CE), consistent with a previously unrecognized, scaffold function of the CLE. Together, these abnormalities result in failure to form normal lamellar bilayers, accounting for the permeability barrier abnormality and clinical phenotype in NIPA-like domain-containing 4 (NIPAL4) deficiency. Thus, NIPAL4 deficiency represents another lipid synthetic ARCI that converges on the CLE (and CE), compromising their putative scaffold function. However, the clinical phenotype only partially improved after normalization of CLE and CE structure with topical omega-O-acylceramide because of ongoing accumulation of toxic metabolites, further evidence that proximal, cytotoxic metabolites contribute to disease pathogenesis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/GC16-25687J" target="_blank" >GC16-25687J: Interdependencies between Inflammatory Processes and Barrier Lipids in Diseased Skin</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
American Journal of Pathology
ISSN
0002-9440
e-ISSN
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Volume of the periodical
188
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
1419-1429
UT code for WoS article
000433524800009
EID of the result in the Scopus database
2-s2.0-85047155439