Fatty acid-binding proteins (FABPs) are postulated to serve as lipid shuttles that solubilize hydrophobic fatty acids and deliver them to appropriate intracellular sites. Epidermal FABP (E-FABP/FABP5) is predominantly expressed in keratinocytes and is overexpressed in the actively proliferating tissue characteristic of psoriasis and wound healing. In this study, we found decreased expression of the differentiation-specific proteins keratin 1, involucrin, and loricrin in E-FABP(-/-) keratinocytes relative to E-FABP(+/+) keratinocytes. We also determined that incorporation of linoleic acid was significantly reduced in E-FABP(-/-) keratinocytes. Although linoleic acid did not directly affect keratinocyte differentiation, keratin 1 expression was induced by the linoleic acid derivative 13(S)-hydroxyoctadecadienoic acid (13(S)-HODE), and this induction was concomitant with increased NF-κB activity. In E-FABP(-/-) keratinocytes, the expression of 13(S)-HODE and the subsequent induction of NF-κB activity was lower than in wild-type keratinocytes. The reduction of linoleic acid in E-FABP(-/-) keratinocytes led to decreased cellular 13(S)-HODE content, resulting in decreased keratin 1 expression through downregulation of NF-κB activity. The regulation of fatty acid metabolism by E-FABP during keratinocyte differentiation suggests that E-FABP may have a role in the pathogenesis of psoriasis.
Fatty acid binding proteins (FABPs) are capable of binding long‐chain FA and are involved in intracellular FA transport and signal transduction. In sebaceous glands, FABP5 is highly expressed in differentiated sebocytes; though, its function remains unclear. In this study, we examined the role of FABP5 in sebocytes using FABP5‐deficient mice. The size of sebaceous glands was significantly reduced, while the sebum volume was increased with altered lipid composition in FABP5‐deficient mice. However, no significant differences were discerned in the expression of proliferation or differentiation markers including Blimp1, c‐myc, Ki67 and peroxisome proliferator‐activated receptors (PPAR)γ between wild‐type and FABP5‐deficient sebaceous glands. The expression of cellular retinoic acid binding protein‐2 (CRABP2) that is a competitor of FABP5 for RA signalling was increased in FABP5‐deficient mice. These results suggest that FABP5 is involved in the regulation of sebaceous gland activity through modulation of cellular lipid signalling and/or metabolism in the sebocytes.
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