Transcriptome analysis of signaling pathways of human peritoneal mesothelial cells in response to different osmotic agents in a peritoneal dialysis solution

BMC Nephrology

Irina Chafeeva¹  Jayachandran N. Kizhakkedathu²  Qiunong Guan³  Ghida Dairi⁴  Caigan Du⁵  Shijian Feng⁶  Bin Liu⁷  Gerald da Roza⁸  Hao Wang⁹  Richard Liggins^1,10 

[1] 0000 0001 2288 9830, grid.17091.3e, Centre for Blood Research, and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;0000 0001 2288 9830, grid.17091.3e, Centre for Blood Research, and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;0000 0001 2288 9830, grid.17091.3e, Department of Chemistry, University of British Columbia, Vancouver, BC, Canada;0000 0001 2288 9830, grid.17091.3e, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada;0000 0001 2288 9830, grid.17091.3e, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada;0000 0000 9137 6644, grid.412832.e, Medicine and Medical Sciences Research Center, Deanship of Scientific Research, Umm Al Qura University, Mecca, Saudi Arabia;0000 0001 2288 9830, grid.17091.3e, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada;0000 0001 0684 7796, grid.412541.7, Jack Bell Research Centre, 2660 Oak Street, V6H 3Z6, Vancouver, BC, Canada;0000 0001 2288 9830, grid.17091.3e, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada;0000 0001 0807 1581, grid.13291.38, Department of Urology, and Laboratory of Reconstructive Urology at the Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China;0000 0001 2288 9830, grid.17091.3e, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada;0000 0004 1757 9434, grid.412645.0, General Hospital of Tianjin Medical University, No.154 Anshan Road, Heping District, 300052, Tianjin, China;0000 0001 2288 9830, grid.17091.3e, Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada;0000 0004 1757 9434, grid.412645.0, General Hospital of Tianjin Medical University, No.154 Anshan Road, Heping District, 300052, Tianjin, China;grid.440037.4, Centre for Drug Research and Development, Vancouver, BC, Canada;

关键词: Osmotic agents;    Hyperbranched polyglycerol;    Glucose;    Transcriptome;    Signaling pathways;    Peritoneal mesothelial cells;   

DOI  :  10.1186/s12882-019-1376-0

来源: publisher

【 摘 要 】

BackgroundGlucose 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.MethodsCultured 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.ResultsThe 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.ConclusionThe 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.

【 授权许可】

CC BY