High glucose concentration-induced expression of pentraxin-3 in a rat model of continuous peritoneal dialysis

Nana Ishimatsu^1,2, Tetsu Miyamoto¹, Hiromichi Ueno¹, Emi Hasegawa¹, Akihiro Kuma¹, Yoko Fujimoto¹, Kenichiro Bando¹, Junichi Nakamata¹, Yumi Furuno¹, Ryota Serino³, Ryoko Baba², Hiroyuki Morimoto², Yoshiaki Doi², Masahito Tamura³ and Yutaka Otsuji<sup>1

1</sup>The Second Department of Internal Medicine, ²Department of Anatomy and ³Kidney Center, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi, Kitakyushu, Japan

Offprint requests to: Tetsu Miyamoto, The Second Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi, Kitakyushu, 807-8555, Japan. e-mail: tetsum@med.uoeh-u.ac.jp

Summary. Background: Continuous exposure to peritoneal dialysis fluids (PDFs) is associated with pathological responses such as persistent micro-inflammation, which leads to ultrafiltration failure. Pentraxin-3 (PTX3), a multifunctional soluble pattern recognition receptor, is produced at sites of inflammation by a wide range of cell types. This study investigates the in vivo expression of PTX3 in the peritoneal membrane of a rat continuous peritoneal dialysis (PD) model, as well as the effect of high glucose on the in vitro expression of PTX3. Methods: The expression of PTX3 was analyzed using RT-PCR, real-time PCR, immunohistochemistry and western blotting in a PD rat model receiving saline or conventional PDF containing 3.86% glucose for 8 weeks. The effects of high glucose on the expression of PTX3 were examined in cultured rat peritoneal mesothelial cells (RPMCs), mouse macrophage-like cells, and mouse fibroblasts. Results: In a rat model of PD, eight-week instillation of the conventional PDF produced increased submesothelial thickening, followed by substantially enhanced PTX3 protein levels in the submesothelial layer of peritoneal membrane. PTX3 was detected in peritoneal mesothelial cells, macrophages and fibroblasts in the thickened submesothelial area. Glucose was found to induce PTX3 protein expression in RPMCs as well as macrophage-like cells and fibroblasts. Conclusion: Continuous exposure to conventional PDF induces PTX3 expression in the peritoneal membrane of rats. High glucose may be involved in the mechanism of PDF-induced local micro-inflammation in the peritoneum. Histol Histopathol 31, 1251-1258 (2016)

Key words: Pentraxin-3, Peritoneal dialysis, Peritoneal fibrosis, Micro-inflammation, Peritoneal mesothelium

DOI: 10.14670/HH-11-756