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Kidney Week

Abstract: SA-PO685

MMP-12 Inhibitor Ameliorates the Peritoneal Fibrosis in a Peritoneal Dialysis (PD) Mouse Model

Session Information

  • Home Dialysis - II
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • Hasegawa, Emi, Kidney Center, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
  • Baba, Ryoko, Sangyo Ika Daigaku, Kitakyushu, Fukuoka, Japan
  • Kokubu, Keiji, Sangyo Ika Daigaku, Kitakyushu, Fukuoka, Japan
  • Shirouzu, Tomohiro, Kidney Center, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
  • Nagai, Yoichiro, Kidney Center, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
  • Ishida, Hiroshi, Kidney Center, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
  • Furuno, Ikutaro, Kidney Center, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
  • Nakazono, Kazutoshi, Kidney Center, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
  • Miyamoto, Tetsu, Kidney Center, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
  • Kataoka, Masaharu, Sangyo Ika Daigaku, Kitakyushu, Fukuoka, Japan
  • Morimoto, Hiroyuki, Sangyo Ika Daigaku, Kitakyushu, Fukuoka, Japan
Background

Continuous exposure to non-physiological fluids during peritoneal dialysis (PD) is associated with pathological responses, such as sustained microinflammation, leading to tissue fibrosis and angiogenesis. We reported that submesothelial expression of matrix metalloproteinase-12 (MMP-12), an elastin proteinase secreted by macrophages, was enhanced by continuous exposure to peritoneal dialysis fluid(PDF). In this study, we investigated the effects of MMP-12 inhibitor on peritoneal fibrosis.

Methods

Morphological changes of the peritoneum in a PD mouse model were histologically analyzed in a peritoneal dialysis fluid (PDF) group (intraperitoneal PDF instillation once a day for 6 weeks), a control group (saline), and a MMP-12 inhibition group (PDF + MMP-12 inhibitor).

Results

Elastica van Gieson staining showed that the elastin just below the mesothelial cell layer was disorganized and fragmented in the PDF group, compared with the control group. Elastin fragments were observed also in collagenous thickened submesothelial tissue in the PDF group, not in the control group. In the MMP-12 inhibition group, no degradation of the elastin or no elastin fragments in submesothelial tissue was observed. Mesothelial cell swelling, peritoneal thickening, and increased collagen fiber expression observed in the PDF group were significantly suppressed in PDF+MMP-12 inhibition group.

Conclusion

The results suggest that MMP-12 induced by PDF instillation could be associated with local microinflammation in the peritoneal tissue, suggesting that MMP-12 may be an therapeutic target to relieve peritoneal damage.