title: A secretome analysis reveals that PPARα is upregulated by fractionated-dose γ-irradiation in three-dimensional keratinocyte cultures.
abstract: Studies have shown that γ-irradiation induces various biological responses, including oxidative stress and apoptosis, as well as cellular repair and immune system responses. However, most such studies have been performed using traditional two-dimensional cell culture systems, which are limited in their ability to faithfully represent in vivo conditions. A three-dimensional (3D) environment composed of properly interconnected and differentiated cells that allow communication and cooperation among cells via secreted molecules would be expected to more accurately reflect cellular responses. Here, we investigated γ-irradiation-induced changes in the secretome of 3D-cultured keratinocytes. An analysis of keratinocyte secretome profiles following fractionated-dose γ-irradiation revealed changes in genes involved in cell adhesion, angiogenesis, and the immune system. Notably, peroxisome proliferator-activated receptor-α (PPARα) was upregulated in response to fractionated-dose γ-irradiation. This upregulation was associated with an increase in the transcription of known PPARα target genes in secretome, including angiopoietin-like protein 4, dermokine and kallikrein-related peptide 12, which were differentially regulated by fractionated-dose γ-irradiation. Collectively, our data imply a mechanism linking γ-irradiation and secretome changes, and suggest that these changes could play a significant role in the coordinated cellular responses to harmful ionizing radiation, such as those associated with radiation therapy. This extension of our understanding of γ-irradiation-induced secretome changes has the potential to improve radiation therapy strategies.
authors.affiliation: Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
authors.forename: Jeeyong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea. Electronic address: yjy_71@kcch.re.kr.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Yi
mesh_terms: D002448:Cell Adhesion / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D005720:Gamma Rays; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D018919:Neovascularization, Physiologic / Q000502:physiology / Q000528:radiation effects; D047495:PPAR gamma / Q000378:metabolism*; D066330:Printing, Three-Dimensional; D020543:Proteome / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology / Q000528:radiation effects
chemical_list: D047495:PPAR gamma; D020543:Proteome
keywords: Keratinocyte; Microarray; PPARα; Secretome; Three-dimensional culture; γ-irradiation