TY - JOUR
T1 - 8s-Lipoxygenase products activate peroxisome proliferator-activated receptor α and induce differentiation in murine keratinocytes
AU - Muga, S. J.
AU - Thuillier, P.
AU - Pavone, A.
AU - Rundhaug, J. E.
AU - Boeglin, W. E.
AU - Jisaka, M.
AU - Brash, A. R.
AU - Fischer, S. M.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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M3 - Article
C2 - 10965849
AN - SCOPUS:0033904659
SN - 1044-9523
VL - 11
SP - 447
EP - 454
JO - Cell Growth and Differentiation
JF - Cell Growth and Differentiation
IS - 8
ER -