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Abstract
Epidermal fatty acid-binding protein (E-FABP) is a lipid carrier, originally discovered in human epidermis. We show that E-FABP is almost exclusively expressed in postmitotic (PM) keratinocytes, corresponding to its localization in the highest suprabasal layers, while it is barely expressed in keratinocyte stem cells (KSC) and transit amplifying (TA) keratinocytes. Transfection of normal human keratinocytes with recombinant (r) E-FABP induces overexpression of K10 and involucrin. On the other hand, E-FABP inhibition by siRNA downregulates K10 and involucrin expression in normal keratinocytes through NF-κB and JNK signalling pathways. E-FABP is highly expressed in psoriatic epidermis, and it is mainly localized in stratum spinosum. Psoriatic PM keratinocytes overexpress E-FABP as compared to the same population in normal epidermis. E-FABP inhibition in psoriatic keratinocytes markedly reduces differentiation, while it upregulates psoriatic markers such as survivin and K16. However, under high-calcium conditions, E-FABP silencing downregulates K10 and involucrin, while survivin and K16 expression is completely abolished. These data strongly indicate that E-FABP plays an important role in keratinocyte differentiation. Moreover, E-FABP modulates differentiation in psoriatic keratinocytes.
Highlights
Epidermal differentiation is a physiological mechanism characterized by morphological changes and by the expression of a variety of markers
Epidermal-Fatty Acid Binding Protein (E-FABP) was mostly expressed in post mitotic (PM) keratinocytes, while it was weakly detectable in transit amplifying (TA) and absent in keratinocyte stem cells (KSC), both at the mRNA and protein level
By separating KSC from TA and PM cells based on β1-integrin expression levels, as previously reported [18,19], we show that E-FABP protein is highly expressed in PM cells, while it is barely detected in TA and KSC
Summary
Epidermal differentiation is a physiological mechanism characterized by morphological changes and by the expression of a variety of markers. Changes in keratinocyte differentiation are associated with variation in lipid composition of epidermal layers [1] During this process, keratinocytes start to express lipid carriers, including high amounts of Epidermal-Fatty Acid Binding Protein (E-FABP) [2]. E-FABP fulfills different roles, including fatty acid transport, control of fatty acids metabolism and cell migration [6]. It regulates cytokine productions [7], and it is related to all-trans retinoic acid sensitivity in cancer cells [8, 9]. A functional role of E-FABP in human keratinocyte differentiation both in normal and psoriatic epidermis remains to be determined.
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