Abstract: SA-PO737

Trehalose Ameliorates Peritoneal Fibrosis through the Induction of Autophagy and the Downregulation of Snail Protein in Peritoneal Mesothelial Cells

Session Information

  • Peritoneal Dialysis - II
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Dialysis

  • 608 Peritoneal Dialysis

Authors

  • Miyake, Taito, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
  • Wada, Takashi, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Sakai, Norihiko, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
  • Kamikawa, Yasutaka, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
  • Kitajima, Shinji, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
  • Toyama, Tadashi, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
  • Hara, Akinori, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
  • Iwata, Yasunori, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
  • Shimizu, Miho, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
  • Furuichi, Kengo, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
Background

Peritoneal fibrosis is a severe complication of peritoneal dialysis, but there are few effective therapies to treat and/or provide for it. Trehalose is a non-reducing disaccharide and can be an osmolyte of peritoneal dialysis solution. Recent studies reveal new biological effects of trehalose as an autophagy inducer and it can be considered to be a hopeful candidate of therapeutic reagent for some diseases. But there are few reports about therapeutic effects of trehalose on fibrotic diseases. We therefore examined if trehalose has anti-fibrotic effects on the peritoneal fibrosis.

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. For in vitro study, we isolated primary mouse peritoneal mesothelial cells to investigate the ability of trehalose to attenuate the profibrotic responses.

Results

CG-induced increases in peritoneal thickness, type I pro-collagen mRNA expression and hydroxyproline content were significantly attenuated in trehalose-treated mice (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. To specifically identify αSMA+ fibroblasts originated from peritoneal mesothelial cells, dual immunostainings of peritoneal sections were performed using anti-Wilms’ tumor 1(WT1) antibody and anti-αSMA antibody. The number of WT1/αSMA dual positive cells in the peritoneum after CG challenges was significantly suppressed by trehalose (n=4). In primary peritoneal mesothelial cells, trehalose attenuates the increase of αSMA and type I pro-collagen mRNA expression induced by TGF-β1, through the induction of autophagy and the downregulation of Snail protein.

Conclusion

Our results suggest that trehalose might be a novel therapeutic reagent for peritoneal fibrosis through the induction of autophagy and the downregulation of Snail protein in peritoneal mesothelial cells.