Abstract
Recent studies using knock-out mice for various secreted phospholipase A2 (sPLA2) isoforms have revealed their non-redundant roles in diverse biological events. In the skin, group IIF sPLA2 (sPLA2-IIF), an "epidermal sPLA2" 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 sPLA2 (sPLA2-IIE) was expressed abundantly in hair follicles and to a lesser extent in basal epidermal keratinocytes in mouse skin. Mice lacking sPLA2-IIE exhibited skin abnormalities distinct from those in mice lacking sPLA2-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 sPLA2-IIE and -IIF were coupled with distinct lipid pathways in the skin. Overall, two skin sPLA2s, hair follicular sPLA2-IIE and epidermal sPLA2-IIF, play non-redundant roles in distinct compartments of mouse skin, underscoring the functional diversity of multiple sPLA2s in the coordinated regulation of skin homeostasis and diseases.
Highlights
Lipids constitute an essential component of skin homeostasis and diseases
In a search of other mouse tissues in which secreted PLA2 (sPLA2)-IIE is expressed under steady-state conditions, we found that Pla2g2e mRNA was uniquely distributed in the uterus and skin at higher levels than in adipose tissue (Fig. 1A)
We have identified sPLA2-IIE as the second sPLA2 that is abundantly expressed in mouse skin
Summary
Expression of sPLA2-IIE in Mouse Skin—We have recently shown that sPLA2-IIE is highly expressed in hypertrophic adipocytes of obese mice [24]. That the upper part of growing hair follicles, where sPLA2-IIE was located (Fig. 2), appeared to be swollen in Pla2g2eϪ/Ϫ mice relative to Pla2g2eϩ/ϩ mice. There were notable reductions of the acyl and plasmalogen forms of LPE in Pla2g2eϪ/Ϫ skin relative to age-matched Pla2g2eϩ/ϩ skin, the levels of other lysophospholipids, including lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC), were not profoundly affected by Pla2g2e deficiency (Fig. 6B). Phospholipid species did not noticeably differ between the genotypes (data not shown), likely because high background levels of phospholipids in membranes of the whole skin masked their local changes by sPLA2s in a subset of cells These results suggest that sPLA2IIE mobilizes various PUFA and LPE species, but with few effects on PUFA metabolites, in mouse skin. The overall enzymatic properties of sPLA2-IIE observed here are roughly reminiscent of those reported by Suzuki et al [23] and are consistent with the lipid profiles that are altered in Pla2g2eϪ/Ϫ skin in vivo (Fig. 6)
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