Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors.
Various common signaling pathways maintain tissue stem cells, including Notch and Wnt/beta-catenin signals. Phosphoinositide-3 kinase (PI3K)/Akt signaling regulates the 'stemness' of several stem cells in culture, specifically in maintaining embryonic stem and neural stem cells, and in deriving embryonic germ cells from primordial germ cells. We examined the effect of Akt signaling in epidermal cells in transgenic mice expressing an Akt-Mer fusion protein whose kinase activity was conditionally activated by treatment with 4-hydroxytamoxifen (4OHT). The topical application of 4OHT to adult skin of the transgenic mice induced new hair growth in resting phase follicles. In addition, the mice showed hyperplasia in interfollicular epidermis (IFE) and hair follicles, which was presumably caused by the extensive proliferation of keratinocytes in basal layer of IFE and outer root sheath of hair follicles, respectively. The progenitor cell population increased consistently in 4OHT-treated transgenic mice. Our results show that PI3K/Akt signaling induces epidermal hyperplasia and proliferation of epidermal progenitors.
Murayama
K
K
Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Kimura
T
T
Tarutani
M
M
Tomooka
M
M
Hayashi
R
R
Okabe
M
M
Nishida
K
K
Itami
S
S
Katayama
I
I
Nakano
T
T
D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000032:analysis; D001665:Binding Sites / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology; D005434:Flow Cytometry; D018859:Hair Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D039503:Integrin alpha6 / Q000032:analysis; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology
D018952:Antigens, CD34; D039503:Integrin alpha6; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D013629:Tamoxifen; C016601:afimoxifene; D000431:Ethanol; D051057:Proto-Oncogene Proteins c-akt