title: Role of NF-κB-p53 crosstalk in ultraviolet A-induced cell death and G1 arrest in human dermal fibroblasts.
abstract: Photoaging is the premature aging of the skin caused by repeated exposure to sunlight and is characterized by a depletion of the dermal extracellular matrix. This depletion is due to the loss of fibroblast cells and their multiple functions. UVA was revealed as a major inducer of photoaging in various clinical studies. As UVA photons have long wavelength spectra, UVA penetrates deeper into the dermis than UVB and UVC, leading to the induction of cell death, the destruction of the dermal extracellular matrix through the induction of matrix metalloproteinase expression, and the repression of collagen expression. However, the exact effects of UVA on the skin remain a matter of debate. Here, we assess cell cycle stage to demonstrate that NF-κB-p53 crosstalk induces apoptosis and growth arrest in UVA-irradiated human dermal fibroblasts. In addition, UVA irradiation led to an increase of NF-κB-HDAC1 complexes, which in turn repressed cyclin D1 expression in UVA-irradiated human dermal fibroblasts. We provide direct evidence that UVA irradiation induces changes in the p53-dependent NF-κB complex that lead to growth arrest and apoptosis through the repression of cyclin D1. These studies uncovered that NF-κB-p53 crosstalk is a key regulator of UVA-dependent growth arrest and apoptosis.
authors.affiliation: Cosmetology Research Institute, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Hwa Jun
authors.initials: HJ
authors.lastname: Cha
authors.forename: Misun
authors.initials: M
authors.lastname: Hong
authors.forename: Yeongmin
authors.initials: Y
authors.lastname: Yoon
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Lee
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D056741:Cyclin D / Q000235:genetics / Q000378:metabolism; D020405:Dermis / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D015595:Skin Aging / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D056741:Cyclin D; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1