Epidermal FABP (FABP5) regulates keratinocyte differentiation by 13(S)-HODE-mediated activation of the NF-κB signaling pathway.
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.
Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
Eisaku
E
Ogawa
Yuji
Y
Owada
Shuntaro
S
Ikawa
Yasuhiro
Y
Adachi
Teie
T
Egawa
Kei
K
Nemoto
Kaori
K
Suzuki
Takanori
T
Hishinuma
Hiroshi
H
Kawashima
Hisatake
H
Kondo
Masahiko
M
Muto
Setsuya
S
Aiba
Ryuhei
R
Okuyama
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D053556:Keratin-1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D019787:Linoleic Acid / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*
C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D053556:Keratin-1; D008041:Linoleic Acids; D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011498:Protein Precursors; C064554:loricrin; C024348:13-hydroxy-9,11-octadecadienoic acid; C032253:involucrin; D019787:Linoleic Acid