title: Fluid dwell impact induces peritoneal fibrosis in the peritoneal cavity reconstructed in vitro.
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.
authors: Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. aokis@cc.saga-u.ac.jp.
authors: Shigehisa
authors: S
authors: Aoki
authors: Department of Urology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. nogman@cc.saga-u.ac.jp.
authors: Mitsuru
authors: M
authors: Noguchi
authors: Division of Animal Sciences, National Institute of Agrobiological Sciences, Ibaraki, Japan.
authors: Toshiaki
authors: T
authors: Takezawa
authors: Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors: Satoshi
authors: S
authors: Ikeda
authors: Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors: Kazuyoshi
authors: K
authors: Uchihashi
authors: Isehara Research Laboratory, Kanto Chemical Co. Inc., Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Kuroyama
authors: Isehara Research Laboratory, Kanto Chemical Co. Inc., Tokyo, Japan.
authors: Tomoyuki
authors: T
authors: Chimuro
authors: Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
authors: Shuji
authors: S
authors: Toda
mesh_terms: D001202:Ascitic Fluid / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D008962:Models, Theoretical; D009569:Nitric Oxide / Q000378:metabolism; D010529:Peritoneal Cavity / Q000473:pathology*; D010530:Peritoneal Dialysis; D056627:Peritoneal Fibrosis / Q000473:pathology*; D010537:Peritoneum / Q000473:pathology*
chemical_list: D009569:Nitric Oxide
keywords: Epithelial–mesenchymal transition; Nitric oxide; Shear stress