| First Author | Hirabayashi T | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14609 | PubMed ID | 28248300 |
| Mgi Jnum | J:240682 | Mgi Id | MGI:5888934 |
| Doi | 10.1038/ncomms14609 | Citation | Hirabayashi T, et al. (2017) PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis. Nat Commun 8:14609 |
| abstractText | 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 omega-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)-omega-hydroxy fatty acids are almost absent with reciprocal increases in their putative precursors, indicating that PNPLA1 catalyses the omega-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. |
