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Fluid dwell impact induces peritoneal fibrosis in the peritoneal cavity reconstructed in vitro

  • Original Article
  • Artificial Kidney / Dialysis
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Abstract

Peritoneal fluid dwell impacts the peritoneum by creating an abnormal physiological microenvironment. Little is known about the precise effects of fluid dwell on the peritoneum, and no adequate in vitro models to analyze the impact of fluid dwell have been established. In this study, we developed a peritoneal fluid dwell model combined with an artificial peritoneal cavity and fluid stirring generation system to clarify the effects of different dwelling solutions on the peritoneum over time. To replicate the peritoneal cavity, we devised a reconstructed peritoneal cavity utilizing a mesothelial layer, endothelial layer, and collagen membrane chamber. The reconstructed peritoneal cavity was infused with Dulbecco’s modified Eagle’s medium, saline, lactated Ringer’s solution or peritoneal dialysis solution with repeated 4-h dwells for 10 or 20 consecutive days. The above-described solutions induced epithelial–mesenchymal transition (EMT) and hyperplasia of mesothelial cells. All solution types modulated nitric oxide synthase activities in mesothelial and endothelial cells and nitric oxide concentrations in dwelling solutions. Inhibition of nitric oxide synthase activity acted synergistically on mesothelial EMT and hyperplasia. The present findings suggest that solutions infused into the peritoneal cavity are likely to affect nitric oxide production in the peritoneum and promote peritoneal fibrosis. Our newly devised peritoneal cavity model should be a promising tool for understanding peritoneal cellular kinetics and homeostasis.

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Acknowledgments

We thank H. Ideguchi, M. Nishida, F. Mutoh, S. Nakahara, T. Takezawa (Teikyo University), and I. Nanbu for excellent technical assistance. We are grateful to Mr. K. Tokaichi for refining the English of the manuscript. This work was supported in part by an Agri-Health Translational Research Project (No. 6110) from the MAFF of Japan and JSPS KAKENHI Grant Number 25461701.

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Authors and Affiliations

  1. Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Shigehisa Aoki, Satoshi Ikeda, Kazuyoshi Uchihashi & Shuji Toda

  2. Department of Urology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Mitsuru Noguchi

  3. Division of Animal Sciences, National Institute of Agrobiological Sciences, Ibaraki, Japan

    Toshiaki Takezawa

  4. Isehara Research Laboratory, Kanto Chemical Co. Inc., Tokyo, Japan

    Hiroyuki Kuroyama & Tomoyuki Chimuro

Authors
  1. Shigehisa Aoki
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  2. Mitsuru Noguchi
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  3. Toshiaki Takezawa
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  4. Satoshi Ikeda
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  5. Kazuyoshi Uchihashi
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  6. Hiroyuki Kuroyama
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  7. Tomoyuki Chimuro
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  8. Shuji Toda
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Correspondence to Shigehisa Aoki or Mitsuru Noguchi.

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Conflicts of interest

H. Kuroyama and T. Chimuro are employees of Kanto Chemical Co. Inc. The other authors declare that they have no conflict of interest.

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Aoki, S., Noguchi, M., Takezawa, T. et al. Fluid dwell impact induces peritoneal fibrosis in the peritoneal cavity reconstructed in vitro. J Artif Organs 19, 87–96 (2016). https://doi.org/10.1007/s10047-015-0864-7

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  • DOI: https://doi.org/10.1007/s10047-015-0864-7

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