ID | 119545 |
Author |
Hakoi, Haruka
Tokushima University
Miki, Yoshimi
Tokushima University|The University of Tokyo
Nomura, Saki
Tokushima University
Nakajima, Kimiko
Kochi University
Terashima-Murase, Chiaki
Nagoya University
Takeichi, Takuya
Nagoya University
Sano, Shigetoshi
Kochi University
Akiyama, Masashi
Nagoya University
Sakasegawa, Shin-ichi
National Institute of Advanced Industrial Science and Technology|Asahi Kasei Pharma Corporation
Murakami, Makoto
The University of Tokyo|Japan Agency for Medical Research and Development
Yamamoto, Kei
Tokushima University|Japan Agency for Medical Research and Development
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Keywords | Group IIF phospholipase A2
Lysoplasmalogen
Thermocrispum lysophospholipase D
Psoriasis
Lipidomics
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Content Type |
Journal Article
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Description | Epidermal lipids play important roles in skin homeostasis and diseases. Psoriasis is an inflammatory disease characterized by keratinocyte hyperproliferation and Th17 immune responses. We previously reported that ethanolamine-type lysoplasmalogen (P-LPE), preferentially produced by group IIF secreted PLA2 (sPLA2-IIF/PLA2G2F) that is expressed in the suprabasal epidermis, promotes epidermal hyperplasia in psoriatic inflammation. Herein, we show that forcible degradation of epidermal P-LPE by topical application of recombinant lysophospholipase D (LyPls-PLD) from Thermocrispum, a lysoplasmalogen-specific hydrolase, attenuated epidermal hyperplasia and inflammation in imiquimod-induced and K5.Stat3C-transgenic mouse psoriasis models. In humans, P-LPE levels were elevated in the tape-stripped stratum corneum of patients with psoriasis. Moreover, in primary cultured human epidermal keratinocytes, aberrant cell proliferation and activation by psoriatic cytokines were sPLA2-IIF/P-LPE-dependent and were suppressed by the addition of LyPls-PLD with a decrease in P-LPE. These findings confirm that the sPLA2-IIF/P-LPE axis in the epidermis indeed regulates psoriasis, that P-LPE is a lipid biomarker that predicts the severity of psoriasis, and that pharmacological removal of this bioactive lipid is useful to prevent the disease. Thus, our study may lead to the development of drug discovery and diagnostic techniques based on this pathway.
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Journal Title |
Biochimie
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ISSN | 16386183
03009084
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NCID | AA11522535
AA00564792
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Publisher | Elsevier|Société Française de Biochimie et Biologie Moléculaire (SFBBM)
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Volume | 215
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Start Page | 75
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End Page | 87
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Published Date | 2023-10-04
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Rights | © 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Author
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departments |
Bioscience and Bioindustry
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