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- Title
PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis.
- Authors
Hirabayashi, Tetsuya; Anjo, Tatsuki; Kaneko, Arisa; Senoo, Yuuya; Shibata, Akitaka; Takama, Hiroyuki; Yokoyama, Kohei; Nishito, Yasumasa; Ono, Tomio; Taya, Choji; Muramatsu, Kazuaki; Fukami, Kiyoko; Muñoz-Garcia, Agustí; Brash, Alan R.; Ikeda, Kazutaka; Arita, Makoto; Akiyama, Masashi; Murakami, Makoto
- 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.
- Publication
Nature Communications, 2017, Vol 8, Issue 3, p14609
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/ncomms14609