title: Protective role of klotho protein on epithelial cells upon co-culture with activated or senescent monocytes.
abstract: Monocytes ensure proper functioning and maintenance of epithelial cells, while good condition of monocytes is a key factor of these interactions. Although, it was shown that in some circumstances, a population of altered monocytes may appear, there is no data regarding their effect on epithelial cells. In this study, using direct co-culture model with LPS-activated and Dox-induced senescent THP-1 monocytes, we reported for the first time ROS-induced DNA damage, reduced metabolic activity, proliferation inhibition and cell cycle arrest followed by p16-, p21- and p27-mediated DNA damage response pathways activation, premature senescence and apoptosis induction in HeLa cells. Also, we show that klotho protein possessing anti-aging and anti-inflammatory characteristics reduced cytotoxic and genotoxic events by inhibition of insulin/IGF-IR and downregulation of TRF1 and TRF2 proteins. Therefore, klotho protein could be considered as a protective factor against changes caused by altered monocytes in epithelial cells.
authors.affiliation: Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland. Electronic address: jennifermytych@gmail.com.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mytych
authors.affiliation: Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Wos
authors.affiliation: Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Solek
authors.affiliation: Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Koziorowski
mesh_terms: D002453:Cell Cycle; D016922:Cellular Senescence; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000090265:Klotho Proteins; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017077:Culture Media, Conditioned; D007328:Insulin; D017526:Receptor, IGF Type 1; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: DNA damage; Klotho; Monocytes-epithelial cells interactions; Stress