Involvement of HIF-1alpha in UVB-induced epidermal hyperplasia.
Keratinocyte overgrowth after UVB exposure is believed to contribute to skin photoageing and cancer development. However, little is known about the transcription factors that epigenetically regulate keratinocyte response to UVB. Recently, HIF-1alpha was found to play a role in epidermal homeostasis by controlling the keratinocyte cell cycle, and thus, we hypothesized that HIF-1alpha is involved in UVB-induced keratinocyte growth. In cultured keratinocytes, HIF-1alpha was found to be down-regulated shortly after UVB exposure and to be involved in UVB-induced proliferation. In mice repeatedly treated with UVB, the epidermis became hyperplasic and keratinocytes lacked HIF-1alpha in nuclei. Based on these results, we suggest that the deregulation of HIF-1alpha is associated with UVB-induced hyperplasia of the epidermis. This work provides insight of the molecular mechanism underlying UV-induced photoageing and skin cancer development.
Cho
Young-Suk
YS
Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
Kim
Chan-Hyung
CH
Park
Jong-Wan
JW
D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D015536:Down-Regulation; D004817:Epidermis / Q000473:pathology* / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015595:Skin Aging / Q000502:physiology; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit