Hair follicular expression and function of group X secreted phospholipase A2 in mouse skin.
Although perturbed lipid metabolism can often lead to skin abnormality, the role of phospholipase A(2) (PLA(2)) in skin homeostasis is poorly understood. In the present study we found that group X-secreted PLA(2) (sPLA(2)-X) was expressed in the outermost epithelium of hair follicles in synchrony with the anagen phase of hair cycling. Transgenic mice overexpressing sPLA(2)-X (PLA2G10-Tg) displayed alopecia, which was accompanied by hair follicle distortion with reduced expression of genes related to hair development, during a postnatal hair cycle. Additionally, the epidermis and sebaceous glands of PLA2G10-Tg skin were hyperplasic. Proteolytic activation of sPLA(2)-X in PLA2G10-Tg skin was accompanied by preferential hydrolysis of phosphatidylethanolamine species with polyunsaturated fatty acids as well as elevated production of some if not all eicosanoids. Importantly, the skin of Pla2g10-deficient mice had abnormal hair follicles with noticeable reduction in a subset of hair genes, a hypoplasic outer root sheath, a reduced number of melanin granules, and unexpected up-regulation of prostanoid synthesis. Collectively, our study highlights the spatiotemporal expression of sPLA(2)-X in hair follicles, the presence of skin-specific machinery leading to sPLA(2)-X activation, a functional link of sPLA(2)-X with hair follicle homeostasis, and compartmentalization of the prostanoid pathway in hair follicles and epidermis.
Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Kei
K
Yamamoto
Yoshitaka
Y
Taketomi
Yuki
Y
Isogai
Yoshimi
Y
Miki
Hiroyasu
H
Sato
Seiko
S
Masuda
Yasumasa
Y
Nishito
Kiyokazu
K
Morioka
Yoshikazu
Y
Ishimoto
Noriko
N
Suzuki
Yasunori
Y
Yokota
Kohji
K
Hanasaki
Yukio
Y
Ishikawa
Toshiharu
T
Ishii
Tetsuyuki
T
Kobayashi
Kiyoko
K
Fukami
Kazutaka
K
Ikeda
Hiroki
H
Nakanishi
Ryo
R
Taguchi
Makoto
M
Murakami
D000505:Alopecia / Q000201:enzymology / Q000235:genetics; D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D018859:Hair Follicle / Q000201:enzymology*; D006706:Homeostasis / Q000502:physiology; D008543:Melanins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010713:Phosphatidylcholines / Q000235:genetics / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000096:biosynthesis* / Q000235:genetics; D011453:Prostaglandins / Q000235:genetics / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D008543:Melanins; D010713:Phosphatidylcholines; D011453:Prostaglandins; D054497:Phospholipases A2, Secretory
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