8s-Lipoxygenase products activate peroxisome proliferator-activated receptor α and induce differentiation in murine keratinocytes

S. J. Muga, P. Thuillier, A. Pavone, J. E. Rundhaug, W. E. Boeglin, M. Jisaka, A. R. Brash, S. M. Fischer

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

To determine the function and mechanism of action of the 8S-lipoxygenase (8-LOX) product of arachidonic acid, 8S-hydroxyeicosatetraenoic acid (8S-HETE), which is normally synthesized only after irritation of the epidermis, transgenic mice with 8-LOX targeted to keratinocytes through the use of a loricrin promoter were generated. Histological analyses showed that the skin, tongue, and stomach of transgenic mice are highly differentiated, and immunoblotting and immunohistochemistries of skin showed higher levels of keratin-1 expression compared with wild-type mice. The labeling index, however, of the transgenic epidermis was twice that of the wild-type epidermis. Furthermore, 8S-HETE treatment of wild-type primary keratinocytes induced keratin-1 expression. Peroxisome proliferator activated receptor α (PPARα) was identified as a crucial component of keratin-1 induction through transient transfection with expression vectors for PPARα, PPARγ, and a dominant-negative PPAR, as well as through the use of known PPAR agonists. From these studies, it is concluded that 8S-HETE plays an important role in keratinocyte differentiation and that at least some of its effects are mediated by PPARα.

Original languageEnglish (US)
Pages (from-to)447-454
Number of pages8
JournalCell Growth and Differentiation
Volume11
Issue number8
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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