title: Effects of intra- and  extracellular factors on anti-aging klotho gene expression.
abstract: Inactivation  of the klotho gene in mice causes serious systemic disorders, resembling  human aging. However, at the molecular level, its action mechanisms are not  well understood. The stimulatory or inhibitory effects of cis- and  trans-regulatory factors on the klotho gene expression are also still  unclear. We studied the effects of intra- and extracellular factors on human klotho gene expression. For this purpose, pHKP-Luc and pHKP-GFP reporter vectors  were constructed with the 2.1-kbp upstream region of human klotho,  covering its promoter region, using luciferase and GFP genes as the reporter. A  series of vectors that have deletions in the upstream region of the klotho gene  were constructed to assay cis-acting factors. Deletion of some parts of the klotho gene upstream region significantly affected reporter gene expression in  HEK293 cells. p16 and p53 proteins inhibited reporter luciferase expression  under the control of human klotho promoter in a dose-dependent manner.  Calcium and phosphate ions stimulated klotho expression. p21, PTH,  IGF-1, and angiotensin-II had no significant effect on klotho expression  in HEK293 cells.
authors.affiliation: Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Marmara University, Haydarpasa, Uskudar, Istanbul, Turkey. kadirturan@marmara.edu.tr
authors.forename: K
authors.initials: K
authors.lastname: Turan
authors.forename: P
authors.initials: P
authors.lastname: Ata
mesh_terms: D000375:Aging / Q000235:genetics; D000804:Angiotensin II / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005966:Glucuronidase / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000090265:Klotho Proteins; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D017384:Sequence Deletion; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D010710:Phosphates; D016159:Tumor Suppressor Protein p53; D000804:Angiotensin II; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; D008156:Luciferases; D005966:Glucuronidase; D000090265:Klotho Proteins; D020741:rho GTP-Binding Proteins; D002118:Calcium