20.500.12556/DiRROS-15448 In vitro and in vivo correlation of skin and cellular responses to nucleic acid delivery Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immuno- genicity of skin, we correlated the effects of pDNA electrotransfer to fibroblasts and keratinocytes to mouse skin using reverse transcription real-time PCR (RT-qPCR) and several types of protein quantification. After pDNA electrotransfer, the mRNAs of the putative DNA sensors DEAD (AspGlu-Ala-Asp) box polypeptide 60 (Ddx60), absent in melanoma 2 (Aim2), Z-DNA binding protein 1 (Zbp1), interferon activated gene 202 (Ifi202), and interferon-inducible protein 204 (Ifi204) were upregulated in keratinocytes, while Ddx60, Zbp1 and Ifi204 were upregulated in fibroblasts. Increased levels of the mRNAs and proteins of several cytokines and chemokines were detected and varied based on cell type. Mouse skin experiments in vivo confirmed our in vitro results with increased expression of putative DNA sensor mRNAs and of the mRNAs and proteins of several cytokines and chemokines. DNA sensors cytokines electrotransfer skin senzorji DNK citokini elektroprenos koža true false true Elsevier Masson SAS Angleški jezik Slovenski jezik by Authors Neznano 2022-09-06 03:35:29 2022-09-06 08:51:13 2022-09-07 03:38:01 0000-00-00 00:00:00 2022 0 0 str. 113088-1-113088-13 Vol. 150 Jun. 2022 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2022-06-01 602.6/.7 0753-3322 10.1016/j.biopha.2022.113088 107308035 https://www.sciencedirect.com/science/article/pii/S0753332222004772 1 6d44eaab-2d73-11ed-bea5-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20431 RAZ_Bosnjak_Masa_2022.pdf RAZ_Bosnjak_Masa_2022.pdf 1 BB681153CA2264247A6621319E566BA2 b8ad6cc75fd6575fe2a7bb550c554a60c42997628c5ec7979a7f3278b7e029e1 76d705e5-2d9c-11ed-bea5-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20432 Onkološki inštitut Ljubljana 0 0 0