Kidney Week

Abstract: SA-PO931

Trehalose Ameliorates Peritoneal Fibrosis Through the Suppression of Fibroblast Proliferation and Extracellular Matrix Production in Fibroblasts

Session Information

• Dialysis: Peritoneal Dialysis - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 703 Dialysis: Peritoneal Dialysis

Authors

• Miyake, Taito, Kanazawa University, Kanazawa, ishikawa, Japan

Taito Miyake,

• Sakai, Norihiko, Kanazawa University, Kanazawa, ishikawa, Japan

Norihiko Sakai,

• Sato, Koichi, Kanazawa University, Kanazawa, ishikawa, Japan

Koichi Sato,

• Sagara, Akihiro, Kanazawa University, Kanazawa, ishikawa, Japan

Akihiro Sagara,

• Kitajima, Shinji, Kanazawa University, Kanazawa, ishikawa, Japan

Shinji Kitajima,

• Toyama, Tadashi, Kanazawa University, Kanazawa, ishikawa, Japan

Tadashi Toyama,

• Hara, Akinori, Kanazawa University, Kanazawa, ishikawa, Japan

Akinori Hara,

• Iwata, Yasunori, Kanazawa University, Kanazawa, ishikawa, Japan

Yasunori Iwata,

• Shimizu, Miho, Kanazawa University, Kanazawa, ishikawa, Japan

Miho Shimizu,

• Furuichi, Kengo, Kanazawa University, Kanazawa, ishikawa, Japan

Kengo Furuichi,

• Wada, Takashi, Kanazawa University, Kanazawa, ishikawa, Japan

Takashi Wada,

Background

Peritoneal fibrosis is a severe complication of peritoneal dialysis, but there are few effective therapies to treat and/or prevent for it. Trehalose is a non-reducing disaccharide and can be an osmolyte of peritoneal dialysis solution. We have previously revealed that trehalose ameliorated peritoneal fibrosis through the induction of autophagy and the downregulation of Snail protein in peritoneal mesothelial cells. In this study, we examined if trehalose also has anti-fibrotic effects on fibroblasts in the peritoneum.

Methods

Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG). 5% trehalose or vehicle (normal saline) was administered by intraperitoneal injection to mice every other day.

Results

Trehalose attenuated CG-induced increases in peritoneal thickness, type I pro-collagen mRNA expression and hydroxyproline content (n=4-9). In addition, CG challenges induced a marked peritoneal accumulation of α smooth muscle actin (αSMA)⁺ fibroblasts that was significantly reduced by trehalose. We next examined fibroblast proliferation induced by CG challenges in ColIα₂-enhanced green fluorescent protein (GFP) transgenic mice. In order to specifically identify proliferating fibroblasts, we double-stained peritoneal sections with anti-PCNA antibody and anti-GFP antibody. The number of PCNA and GFP dual positive proliferating fibroblasts in the peritoneal tissue after CG challenges was significantly increased in the vehicle group as compared to the trehalose group, as was the percentage of proliferating fibroblasts among total fibroblasts. We also performed an in vitro study to confirm the effects of trehalose on the proliferation of fibroblasts. TGF-β₁ induced fibroblast proliferation; however, trehalose suppressed the fibroblast proliferation in a dose-dependent manner. In addition, trehalose attenuated αSMA, ColIα₁, Col3α₁ and fibronectin mRNA expression induced by TGF-β₁.

Conclusion

Our results suggest that trehalose might be a novel therapeutic reagent for peritoneal fibrosis through the suppression of fibroblasts proliferation and extracellular matrix production in fibroblasts.