@article{3086947, title = "The family of 14-3-3 proteins and specifically 14-3-3σ are up-regulated during the development of renal pathologies", author = "Rizou, M. and Frangou, E.A. and Marineli, F. and Prakoura, N. and Zoidakis, J. and Gakiopoulou, H. and Liapis, G. and Kavvadas, P. and Chatziantoniou, C. and Makridakis, M. and Vlahou, A. and Boletis, J. and Vlahakos, D. and Goumenos, D. and Daphnis, E. and Iatrou, C. and Charonis, A.S.", journal = "Journal of Cellular and Molecular Medicine", year = "2018", volume = "22", number = "9", pages = "4139-4149", publisher = "Blackwell Publishing Inc.", issn = "1582-1838, 1582-4934", doi = "10.1111/jcmm.13691", keywords = "calreticulin; complementary DNA; immunoglobulin A; messenger RNA; peptides and proteins; protein 14 3 3; stratifin; transcription factor HIF1 alpha; unclassified drug; calreticulin; calreticulin, human; exoribonuclease; HIF1A protein, human; hypoxia inducible factor 1alpha; isoenzyme; protein 14 3 3; SFN protein, human; tumor marker, animal experiment; animal model; animal tissue; Article; cell culture; chromatin immunoprecipitation; controlled study; densitometry; experimental glomerulonephritis; gene overexpression; homeostasis; housekeeping gene; human; human cell; hypoxia; immunoglobulin A nephropathy; immunohistochemistry; kidney fibrosis; kidney tubule epithelium; male; matrix assisted laser desorption ionization time of flight mass spectrometry; mouse; nephrectomy; nephrotoxicity; nonhuman; priority journal; protein expression; proteomics; real time polymerase chain reaction; reperfusion injury; upregulation; ureter obstruction; Western blotting; animal; C57BL mouse; cell line; chronic kidney failure; disease model; epithelium cell; fibrosis; gene expression regulation; genetics; kidney tubule; membranous glomerulonephritis; metabolism; pathology; procedures; promoter region; signal transduction, 14-3-3 Proteins; Animals; Biomarkers, Tumor; Calreticulin; Cell Line; Disease Models, Animal; Epithelial Cells; Exoribonucleases; Fibrosis; Gene Expression Regulation; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Isoenzymes; Kidney Tubules; Male; Mice; Mice, Inbred C57BL; Promoter Regions, Genetic; Proteomics; Renal Insufficiency, Chronic; Reperfusion Injury; Signal Transduction; Ureteral Obstruction", abstract = "Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up-regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia-reperfusion. In all these models, the 14-3-3σ isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia-induced transcription factor HIF1α is specifically associated with the promoter region of the 14-3-3σ gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3σ in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14-3-3σ in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine." }