title: Epithelial-to-mesenchymal transition and slit function of mesothelial cells are regulated by the cross talk between mesothelial cells and endothelial cells.
abstract: Peritoneal dysfunction is a major factor leading to treatment failure of peritoneal dialysis (PD). However, the precise mechanism of the peritoneal diffusion changes related to PD remains to be elucidated. To this end, we have established a novel peritoneal diffusion model in vitro, which consists of a three-dimensional culture system using a collagen vitrigel membrane chamber and a fluid-stream generation system. This artificial peritoneal model revealed that high-glucose culture medium and fluid flow stress promoted the epithelial-mesenchymal transition (EMT) process of mesothelial cells and that endothelial cells inhibited this mesothelial EMT process. Mesothelial cells in the EMT state showed high expression of connective tissue growth factor and low expression of bone morphogenic protein-7, while non-EMT mesothelial cells showed the opposite expression pattern of these two proteins. In addition, these protein expressions were dependent on the presence of endothelial cells in the model. Our model revealed that the endothelial slit function was predominantly dependent on the covering surface area, while the mesothelial layer possessed a specific barrier function for small solutes independently of the surface area. Notably, a synergic barrier effect of mesothelial cells and endothelial cells was present with low-glucose pretreatment, but high-glucose pretreatment abolished this synergic effect. These findings suggest that the mesothelial slit function is not only regulated by the high-glucose-induced EMT process but is also affected by an endothelial paracrine effect. This peritoneal diffusion model could be a promising tool for the development of PD.
authors.affiliation: Dept. of Pathology and Microbiology, Faculty of Medicine, Saga Univ., 5-1-1 Nabeshima, Saga 849-8501, Japan. aokis@cc.saga-u.ac.jp.
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Aoki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takezawa
authors.forename: Ayumi
authors.initials: A
authors.lastname: Oshikata-Miyazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuroyama
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Chimuro
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oguchi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Noguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Narisawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
mesh_terms: D002450:Cell Communication / Q000502:physiology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D008954:Models, Biological; D010537:Peritoneum
chemical_list: D003094:Collagen
keywords: collagen vitrigel membrane; epithelial-mesenchymal transition; peritoneal permeability