title: UVB irradiation regulates ERK1/2- and p53-dependent thrombomodulin expression in human keratinocytes.
abstract: Thrombomodulin (TM) is highly expressed in endothelial cells and acts as a natural anticoagulation factor to maintain circulation homeostasis. TM is an interesting molecule with many physiological functions, including anti-inflammation, anti-thrombosis, and carcinogenesis inhibition. TM can also be detected on the spinous layer of epidermal keratinocytes. However, the role of epidermal TM is still under investigation. In this study, we investigated keratinocyte TM expression and regulation in response to sub-cytotoxic ultraviolet B (UVB) irradiation. Oxidative stress was assessed with DCF and the results revealed that UVB irradiation significantly and dose-dependently augmented reactive oxygen species (ROS) production in HaCaT cells. In addition, low-dose UVB irradiation decreased TM mRNA and protein levels. Blocking ROS production and ERK activation prevented UVB-induced TM down-regulation. The nuclear p53 accumulation and TM promoter binding was observed within 3 h after UVB exposure. Small interfering RNA-mediated p53 knockdown disrupted the UVB-mediated TM protein down-regulation. Our study demonstrates that UVB irradiation results in ROS accumulation and ERK activation, which causes the nuclear p53 accumulation and TM promoter binding to inhibit TM expression. This study provides novel evidence demonstrating that p53 serves as a key regulator of keratinocyte TM expression.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung, Taiwan. lchuang@mail.cmu.edu.tw
authors.forename: Huey-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Tsong-Min
authors.initials: TM
authors.lastname: Chang
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
authors.forename: Hsin-Yun
authors.initials: HY
authors.lastname: Wen
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D018180:Thrombomodulin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C546931:THBD protein, human; D018180:Thrombomodulin; D016159:Tumor Suppressor Protein p53; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3