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Transcriptome analysis of signaling pathways of human peritoneal mesothelial cells in response to different osmotic agents in a peritoneal dialysis solution Liu, Bin; Feng, Shijian; Dairi, Ghida; Guan, Qiunong; Chafeeva, Irina; Wang, Hao; Liggins, Richard; da Roza, Gerald; Kizhakkedathu, Jayachandran N.; Du, Caigan

Abstract

Background: Glucose is a primary osmotic agent in peritoneal dialysis (PD) solutions, but its long-term use causes structural alteration of the peritoneal membrane (PM). Hyperbranched polyglycerol (HPG) is a promising alternative to glucose. This study was designed to compare the cellular responses of human peritoneal mesothelial cells (HPMCs) to these two different osmotic agents in a hypertonic solution using transcriptome analysis. Methods: Cultured HPMCs were repeatedly exposed to HPG-based or Physioneal 40 (PYS, glucose 2.27%) hypertonic solutions. Transcriptome datasets were produced using Agilent SurePrint G3 Human GE 8 × 60 microarray. Cellular signaling pathways were examined by Ingenuity Pathway Analysis (IPA). Protein expression was examined by flow cytometry analysis and Western blotting. Results: The HPG-containing solution was better tolerated compared with PYS, with less cell death and disruption of cell transcriptome. The levels of cell death in HPG- or PYS- exposed cells were positively correlated with the number of affected transcripts (HPG: 128 at day 3, 0 at day 7; PYS: 1799 at day 3, 212 at day 7). In addition to more affected “biosynthesis” and “cellular stress and death” pathways by PYS, both HPG and PYS commonly affected “sulfate biosynthesis”, “unfolded protein response”, “apoptosis signaling” and “NRF2-mediated oxidative stress response” pathways at day 3. PYS significantly up-regulated HLA-DMB and MMP12 in a time-dependent manner, and stimulated T cell adhesion to HPMCs. Conclusion: The lower cytotoxicity of hypertonic HPG solution is in agreement with its transient and minimal impact on the pathways for the “biosynthesis of cell constituents” and the “cellular stress and death”. The significant up-regulation of HLA-DMB and MMP12 by PYS may be part of its initiation of immune response in the PM.

Item Metadata

Title
Transcriptome analysis of signaling pathways of human peritoneal mesothelial cells in response to different osmotic agents in a peritoneal dialysis solution
Creator
Liu, Bin; Feng, Shijian; Dairi, Ghida; Guan, Qiunong; Chafeeva, Irina; Wang, Hao; Liggins, Richard; da Roza, Gerald; Kizhakkedathu, Jayachandran N.; Du, Caigan
Contributor
University of British Columbia. Centre for Blood Research; University of British Columbia. Centre for Drug Research and Development
Publisher
BioMed Central
Date Issued
2019-05-21
Description
Background: Glucose is a primary osmotic agent in peritoneal dialysis (PD) solutions, but its long-term use causes structural alteration of the peritoneal membrane (PM). Hyperbranched polyglycerol (HPG) is a promising alternative to glucose. This study was designed to compare the cellular responses of human peritoneal mesothelial cells (HPMCs) to these two different osmotic agents in a hypertonic solution using transcriptome analysis. Methods: Cultured HPMCs were repeatedly exposed to HPG-based or Physioneal 40 (PYS, glucose 2.27%) hypertonic solutions. Transcriptome datasets were produced using Agilent SurePrint G3 Human GE 8 × 60 microarray. Cellular signaling pathways were examined by Ingenuity Pathway Analysis (IPA). Protein expression was examined by flow cytometry analysis and Western blotting. Results: The HPG-containing solution was better tolerated compared with PYS, with less cell death and disruption of cell transcriptome. The levels of cell death in HPG- or PYS- exposed cells were positively correlated with the number of affected transcripts (HPG: 128 at day 3, 0 at day 7; PYS: 1799 at day 3, 212 at day 7). In addition to more affected “biosynthesis” and “cellular stress and death” pathways by PYS, both HPG and PYS commonly affected “sulfate biosynthesis”, “unfolded protein response”, “apoptosis signaling” and “NRF2-mediated oxidative stress response” pathways at day 3. PYS significantly up-regulated HLA-DMB and MMP12 in a time-dependent manner, and stimulated T cell adhesion to HPMCs. Conclusion: The lower cytotoxicity of hypertonic HPG solution is in agreement with its transient and minimal impact on the pathways for the “biosynthesis of cell constituents” and the “cellular stress and death”. The significant up-regulation of HLA-DMB and MMP12 by PYS may be part of its initiation of immune response in the PM.
Subject
Osmotic agents; Hyperbranched polyglycerol; Glucose; Transcriptome; Signaling pathways; Peritoneal mesothelial cells
Genre
Article
Type
Text
Language
eng
Date Available
2019-05-21
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0378893
URI
http://hdl.handle.net/2429/70229
Affiliation
Medicine, Faculty of; Science, Faculty of; Other UBC; Non UBC; Chemistry, Department of; Medicine, Department of; Nephrology, Division of; Pathology and Laboratory Medicine, Department of; Urologic Sciences, Department of
Citation
BMC Nephrology. 2019 May 21;20(1):181
Publisher DOI
10.1186/s12882-019-1376-0
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)