PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis
| Autor: | Tatsuki Anjo, Akitaka Shibata, Kiyoko Fukami, Tomio Ono, Agustí Muñoz-Garcia, Arisa Kaneko, Makoto Murakami, Tetsuya Hirabayashi, Choji Taya, Yasumasa Nishito, Kohei Yokoyama, Kazuaki Muramatsu, Kazutaka Ikeda, Masashi Akiyama, Makoto Arita, Yuuya Senoo, Hiroyuki Takama, Alan R. Brash |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Keratinocytes
0301 basic medicine Cellular differentiation Science General Physics and Astronomy Biology Phospholipase Ceramides Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biosynthesis Congenital ichthyosis medicine Stratum corneum Animals Humans Skin Transepidermal water loss Multidisciplinary integumentary system Ichthyosis Cell Differentiation Lipase General Chemistry 1-Acylglycerol-3-Phosphate O-Acyltransferase medicine.disease Mice Inbred C57BL Phenotype 030104 developmental biology medicine.anatomical_structure Animals Newborn Biochemistry chemistry 030220 oncology & carcinogenesis Epidermis |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-13 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Loss-of-function mutations in PNPLA1, a gene encoding an enzyme with unknown function, cause dry and scaling skin in humans. Using mouse models with PNPLA1 deficiency, the authors show that PNPLA1 participates in the biosynthesis of acylceramide, a lipid component essential for skin barrier function. |
| Databáze: | OpenAIRE |
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