Abstract：
:Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. Global or keratinocyte-specific Pnpla1-deficient neonates die due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and aberrant keratinocyte differentiation. In Pnpla1-/- epidermis, unique linoleate-containing lipids including acylceramides, acylglucosylceramides and (O-acyl)-ω-hydroxy fatty acids are almost absent with reciprocal increases in their putative precursors, indicating that PNPLA1 catalyses the ω-O-esterification with linoleic acid to form acylceramides. Moreover, acylceramide supplementation partially rescues the altered differentiation of Pnpla1-/- keratinocytes. Our findings provide valuable insight into the skin barrier formation and ichthyosis development, and may contribute to novel therapeutic strategies for treatment of epidermal barrier defects.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Hirabayashi T,Anjo T,Kaneko A,Senoo Y,Shibata A,Takama H,Yokoyama K,Nishito Y,Ono T,Taya C,Muramatsu K,Fukami K,Muñoz-Garcia A,Brash AR,Ikeda K,Arita M,Akiyama M,Murakami Mdoi
10.1038/ncomms14609subject
Has Abstractpub_date
2017-03-01 00:00:00pages
14609issn
2041-1723pii
ncomms14609journal_volume
8pub_type
杂志文章abstract：:Recent studies of thermal transport in nanomaterials have demonstrated the breakdown of Fourier's law through observations of ballistic transport. Despite its unique features, another instance of the breakdown of Fourier's law, hydrodynamic phonon transport, has drawn less attention because it has been observed only a...
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更新日期：2016-02-04 00:00:00
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更新日期：2018-08-02 00:00:00
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更新日期：2014-01-01 00:00:00
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更新日期：2019-10-18 00:00:00
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pub_type： 已发布勘误
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更新日期：2020-02-24 00:00:00
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pub_type： 杂志文章
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