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Deletion of NRF2 disturbs composition, morphology, and differentiation of the murine tail epidermis in chronological aging

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F23%3A10471662" target="_blank" >RIV/00216208:11160/23:10471662 - isvavai.cz</a>

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Rm14ptyusA" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Rm14ptyusA</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1002/biof.1941" target="_blank" >10.1002/biof.1941</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Deletion of NRF2 disturbs composition, morphology, and differentiation of the murine tail epidermis in chronological aging

  • Original language description

    NRF2 is a master regulator of the cellular protection against oxidative damage in mammals and of multiple pathways relevant in the mammalian aging process. In the epidermis of the skin NRF2 contributes additionally to the formation of an antioxidant barrier to protect from environmental insults and is involved in the differentiation process of keratinocytes. In chronological aging of skin, the capacity for antioxidant responses and the ability to restore homeostasis after damage are impaired. Surprisingly, in absence of extrinsic stressors, NRF2 deficient mice do not show any obvious skin phenotype, not even at old age. We investigated the differences in chronological epidermal aging of wild type and NRF2-deficient mice to identify the changes in aged epidermis that may compensate for absence of this important transcriptional regulator. While both genotypes showed elevated epidermal senescence markers (increased Lysophospholipids, decreased LaminB1 expression), the aged NRF2 deficient mice displayed disturbed epidermal differentiation manifested in irregular keratin 10 and loricrin expression. The tail skin displayed less age-related epidermal thinning and a less pronounced decline in proliferating basal epidermal cells compared to the wildtype controls. The stratum corneum lipid composition also differed, as we observed elevated production of barrier protective linoleic acid (C18:2) and reduced abundance of longer chain saturated lignoceric acid (C24:0) among the stratum corneum fatty acids in the aged NRF2-deficient mice. Thus, despite epidermal differentiation being disturbed in aged NRF2-deficient animals in homeostasis, adaptations in keratinocyte proliferation and barrier lipid synthesis could explain the lack of a more severe phenotype.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30104 - Pharmacology and pharmacy

Result continuities

  • Project

    <a href="/en/project/GF22-20839K" target="_blank" >GF22-20839K: Novel Insights into the Nanostructure of the Skin Lipid Barrier by Biophysical Methods</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2023

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    BioFactors

  • ISSN

    0951-6433

  • e-ISSN

    1872-8081

  • Volume of the periodical

    49

  • Issue of the periodical within the volume

    3

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    15

  • Pages from-to

    684-698

  • UT code for WoS article

    000932826200001

  • EID of the result in the Scopus database

    2-s2.0-85147924345