The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and hyperplasia

Yamamoto, Kei; Miki, Yoshimi; Sato, Mariko; Taketomi, Yoshitaka; Nishito, Yasumasa; Taya, Choji; Muramatsu, Kazuaki; Ikeda, Kazutaka; Nakanishi, Hiroki; Taguchi, Ryo; Kambe, Naotomo; Kabashima, Kenji; Lambeau, Gérard; Gelb, Michael H.; Murakami, Makoto

doi:10.1084/jem.20141904

Cited by 82 publications

(140 citation statements)

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“…As reported previously (19), Pla2g2f mRNA (encoding sPLA 2 -IIF) was expressed abundantly in mouse dorsal skin throughout the peri-to postnatal period (Fig. 1B).…”

Section: Resultssupporting

confidence: 85%

“…As expected (19), Pla2g2f was distributed in the epidermal fraction almost exclusively, whereas Pla2g2e was expressed in both fractions, with more abundant expression in the hair follicle fraction than in the epidermal fraction (Fig. 1C).…”

Section: Resultssupporting

confidence: 81%

“…1C). Expression levels of other sPLA 2 s (IB, IID, and V) in hair follicles were minimal (19). Thus, sPLA 2 -IIE is the predominant sPLA 2 expressed in hair follicles during anagen.…”

Section: Resultsmentioning

confidence: 91%

“…We have recently demonstrated that group IIF sPLA 2 (sPLA 2 -IIF) is expressed predominantly in the suprabasal epidermis and that its genetic deletion perturbs keratinocyte differentiation and activation, particularly under pathological conditions such as psoriasis and skin cancer (19). This action of sPLA 2 -IIF as an "epidermal sPLA 2 " depends at least in part on the generation of plasmalogen lysophosphatidylethanolamine (P-LPE; lysoplasmalogen), a unique lysophospholipid that can promote keratinocyte activation and epidermal hyperplasia.…”

mentioning

confidence: 99%

“…This action of sPLA 2 -IIF as an "epidermal sPLA 2 " depends at least in part on the generation of plasmalogen lysophosphatidylethanolamine (P-LPE; lysoplasmalogen), a unique lysophospholipid that can promote keratinocyte activation and epidermal hyperplasia. Beyond sPLA 2 -IIF, transgenic overexpression of sPLA 2 -IIA or -X causes alopecia and epidermal hyperplasia (20,21), although endogenous expression of these two sPLA 2 s as well as sPLA 2 -IB, -IID, and -V in mouse skin is low or almost undetectable (19). sPLA 2 -IIE is an isoform structurally most homologous to sPLA 2 -IIA (22,23).…”

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confidence: 99%

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Expression and Function of Group IIE Phospholipase A2 in Mouse Skin

Yamamoto

Miki²,

Sato³

et al. 2016

Journal of Biological Chemistry

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Recent studies using knock-out mice for various secreted phospholipase A 2 (sPLA 2 ) isoforms have revealed their non-redundant roles in diverse biological events. In the skin, group IIF sPLA 2 (sPLA 2 -IIF), an "epidermal sPLA 2 " expressed in the suprabasal keratinocytes, plays a fundamental role in epidermal-hyperplasic diseases such as psoriasis and skin cancer. In this study, we found that group IIE sPLA 2 (sPLA 2 -IIE) was expressed abundantly in hair follicles and to a lesser extent in basal epidermal keratinocytes in mouse skin. Mice lacking sPLA 2 -IIE exhibited skin abnormalities distinct from those in mice lacking sPLA 2 -IIF, with perturbation of hair follicle ultrastructure, modest changes in the steady-state expression of a subset of skin genes, and no changes in the features of psoriasis or contact dermatitis. Lipidomics analysis revealed that sPLA 2 -IIE and -IIF were coupled with distinct lipid pathways in the skin. Overall, two skin sPLA 2 s, hair follicular sPLA 2 -IIE and epidermal sPLA 2 -IIF, play non-redundant roles in distinct compartments of mouse skin, underscoring the functional diversity of multiple sPLA 2 s in the coordinated regulation of skin homeostasis and diseases.Lipids constitute an essential component of skin homeostasis and diseases. The epidermis is a highly organized stratified epithelium having four distinctive layers comprising the innermost stratum basale, the stratum spinosum, the stratum granulosum, and the outermost stratum corneum (SC) 2 (1). The hair follicle, a skin appendage formed by interactions between epidermal keratinocytes committed to hair follicle differentiation and dermal fibroblasts committed to formation of the dermal papilla, undergoes repeated cycles of growth (anagen), regression (catagen), and rest (telogen) during life span (2). Nutritional insufficiency of essential fatty acids causes epidermal and hair abnormalities (1), and genetic mutations in several steps of skin lipid metabolism variably and often severely affect SC barrier function or hair cycling, thereby causing or exacerbating skin disorders such as ichthyosis, psoriasis, atopic dermatitis, and alopecia (3-6). Linoleic acid (LA), by far the most abundant polyunsaturated fatty acid (PUFA) in the SC, is crucial for the formation of acylceramide, an essential component of the cornified lipid envelope (7,8). Fatty acids have also been implicated in SC acidification (9 -11). Furthermore, dysregulated production of lipid mediators derived from PUFAs or lysophospholipids can be linked to skin disorders such as hair loss, epidermal hyperplasia, dermatitis, and cancer (6, 12, 13).Phospholipase A 2 (PLA 2 ) enzymes hydrolyze the sn-2 position of phospholipids to release fatty acids and lysophospholipids, which act as precursors of a variety of lipid mediators. Of the PLA 2 enzymes, cytosolic PLA 2 ␣ plays a central role in eicosanoid generation by selectively releasing arachidonic acid (AA) (14, 15), and Ca 2ϩ -independent PLA 2 s are involved in energy metabolism and neurodegeneration (16,17). ...

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“…As reported previously (19), Pla2g2f mRNA (encoding sPLA 2 -IIF) was expressed abundantly in mouse dorsal skin throughout the peri-to postnatal period (Fig. 1B).…”

Section: Resultssupporting

confidence: 85%

Section: Resultssupporting

confidence: 81%

“…1C). Expression levels of other sPLA 2 s (IB, IID, and V) in hair follicles were minimal (19). Thus, sPLA 2 -IIE is the predominant sPLA 2 expressed in hair follicles during anagen.…”

Section: Resultsmentioning

confidence: 91%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Expression and Function of Group IIE Phospholipase A2 in Mouse Skin

Yamamoto

Miki²,

Sato³

et al. 2016

Journal of Biological Chemistry

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Plasmalogen homeostasis – regulation of plasmalogen biosynthesis and its physiological consequence in mammals

Honsho

Fujiki

2017

FEBS Letters

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Plasmalogens, mostly ethanolamine‐containing alkenyl ether phospholipids, are a major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of peroxisome biogenesis‐defective patients suggests that the de novo synthesis of plasmalogens plays a pivotal role in its homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the stability of fatty acyl‐CoA reductase 1 on peroxisomal membranes, a rate‐limiting enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of plasma membranes. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis by altering the stability of squalene monooxygenase, a key enzyme in cholesterol biosynthesis, implying physiological consequences of plasmalogen homeostasis with respect to cholesterol metabolism in cells, as well as in organs such as the liver.

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Roles of lipid mediators in early pregnancy events

Aikawa,

Hirota

2024

Reprod Medicine & Biology

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BackgroundEarly pregnancy events, including embryo implantation, are critical for maintaining a healthy pregnancy and facilitating childbirth. Despite numerous signaling pathways implicated in establishing early pregnancy, a comprehensive understanding of implantation remains elusive.MethodsThis paper provides a comprehensive review of the current research on lipids in the context of early pregnancy, with a particular focus on feto‐maternal communications.Main FindingsEmbryo implantation entails direct interaction between uterine tissues and embryos. Introducing embryos triggers significant changes in uterine epithelial morphology and stromal differentiation, facilitating embryo implantation through communication with uterine tissue. Studies employing genetic models and chemical compounds targeting enzymes and receptors have elucidated the crucial roles of lipid mediators—prostaglandins, lysophosphatidic acid, sphingosine‐1‐phosphate, and cannabinoids—in early pregnancy events.ConclusionGiven the high conservation of lipid synthases and receptors across species, lipid mediators likely play pivotal roles in rodents and humans. Further investigations into lipids hold promise for developing novel diagnostic and therapeutic approaches for infertility in humans.

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The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and hyperplasia

Abstract: Yamamoto et al. report that PLA2G2F represents a previously unrecognized regulator of skin pathophysiology, and point to this enzyme as a novel drug target for epidermal-hyperplasic diseases.

Cited by 82 publications

References 56 publications

Expression and Function of Group IIE Phospholipase A2 in Mouse Skin

Expression and Function of Group IIE Phospholipase A2 in Mouse Skin

Plasmalogen homeostasis – regulation of plasmalogen biosynthesis and its physiological consequence in mammals

Roles of lipid mediators in early pregnancy events

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