Cross-omics comparison of stress responses in mesothelial cells exposed to heat- versus filter-sterilized peritoneal dialysis fluids.
Recent research suggests that cytoprotective responses, such as expression of heat-shock proteins, might be inadequately induced in mesothelial cells by heat-sterilized peritoneal dialysis (PD) fluids. This study compares transcriptome data and multiple protein expression profiles for providing new insight into regulatory mechanisms. Two-dimensional difference gel electrophoresis (2D-DIGE) based proteomics and topic defined gene expression microarray-based transcriptomics techniques were used to evaluate stress responses in human omental peritoneal mesothelial cells in response to heat- or filter-sterilized PD fluids. Data from selected heat-shock proteins were validated by 2D western-blot analysis. Comparison of proteomics and transcriptomics data discriminated differentially regulated protein abundance into groups depending on correlating or noncorrelating transcripts. Inadequate abundance of several heat-shock proteins following exposure to heat-sterilized PD fluids is not reflected on the mRNA level indicating interference beyond transcriptional regulation. For the first time, this study describes evidence for posttranscriptional inadequacy of heat-shock protein expression by heat-sterilized PD fluids as a novel cytotoxic property. Cross-omics technologies introduce a novel way of understanding PDF bioincompatibility and searching for new interventions to reestablish adequate cytoprotective responses.
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria ; Zytoprotec GmbH, 1090 Vienna, Austria.
Klaus
K
Kratochwill
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria ; Department of Nephrology and Medical Intensive Care, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
Thorsten O
TO
Bender
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria ; Zytoprotec GmbH, 1090 Vienna, Austria.
Anton M
AM
Lichtenauer
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria ; Zytoprotec GmbH, 1090 Vienna, Austria.
Rebecca
R
Herzog
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria.
Silvia
S
Tarantino
Zytoprotec GmbH, 1090 Vienna, Austria.
Katarzyna
K
Bialas
Department of Nephrology and Medical Intensive Care, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
Achim
A
Jörres
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria.
Christoph
C
Aufricht
D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000009:adverse effects* / Q000737:chemistry / Q000302:isolation & purification; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005374:Filtration; D020869:Gene Expression Profiling / Q000379:methods; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013242:Sterilization; D018511:Systems Integration; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods
D015314:Dialysis Solutions; D006360:Heat-Shock Proteins