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Buffer-dependent regulation of aquaporin-1 expression and function in human peritoneal mesothelial cells

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Abstract

Background

Biocompatible peritoneal dialysis fluids (PDF) are buffered with lactate and/or bicarbonate. We hypothesized that the reduced toxicity of the biocompatible solutions might unmask specific effects of the buffer type on mesothelial cell functions.

Methods

Human peritoneal mesothelial cells (HPMC) were incubated with bicarbonate (B-)PDF or lactate-buffered (L-)PDF followed by messenger RNA (mRNA) and protein analysis. Gene silencing was achieved using small interfering RNA (siRNA), functional studies using Transwell culture systems, and monolayer wound-healing assays.

Results

Incubation with B-PDF increased HPMC migration in the Transwell and monolayer wound-healing assay to 245 ± 99 and 137 ± 11% compared with L-PDF. Gene silencing showed this effect to be entirely dependent on the expression of aquaporin-1 (AQP-1) and independent of AQP-3. Exposure of HPMC to B-PDF increased AQP-1 mRNA and protein abundance to 209 ± 80 and 197 ± 60% of medium control; the effect was pH dependent. L-PDF reduced AQP-1 mRNA. Addition of bicarbonate to L-PDF increased AQP-1 abundance by threefold; mRNA half-life remained unchanged. Immunocytochemistry confirmed opposite changes of AQP-1 cell-membrane abundance with B-PDF and L-PDF.

Conclusions

Peritoneal mesothelial AQP-1 abundance and migration capacity is regulated by pH and buffer agents used in PD solutions. In vivo studies are required to delineate the impact with respect to long-term peritoneal membrane integrity and function.

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Acknowledgements

We thank Prof. Dr. Jutta Passlick-Deetjen, University of Düsseldorf, for scientific advice.

Disclosure

The project was supported by Fresenius Medical Care, Bad Homburg, Germany.

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany

    Yihui Zhai, Jacek Bloch, Meike Hömme, Julia Schaefer, Bärbel Philippin, Franz Schaefer & Claus P. Schmitt

  2. Department of Nephrology, Children’s Hospital of Fudan University, Shanghai, China

    Yihui Zhai

  3. Department of Surgery, University of Heidelberg, Heidelberg, Germany

    Thilo Hackert

  4. Department of Internal Medicine, Division of Nephrology, University of Heidelberg, Heidelberg, Germany

    Vedat Schwenger

  5. Department of Pediatric Nephrology, Gastroenterology and Metabolic Diseases, Children’s Hospital, Hannover Medical School, Hannover, Germany

    Meike Hömme

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  1. Yihui Zhai
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Correspondence to Claus P. Schmitt.

Additional information

Yihui Zhai and Jacek Bloch contributed equally to this manuscript

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Zhai, Y., Bloch, J., Hömme, M. et al. Buffer-dependent regulation of aquaporin-1 expression and function in human peritoneal mesothelial cells. Pediatr Nephrol 27, 1165–1177 (2012). https://doi.org/10.1007/s00467-012-2120-1

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  • DOI: https://doi.org/10.1007/s00467-012-2120-1

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