Abstract: SA-PO947
Deletion of Matrix Metalloproteinase 10 Ameliorates Peritoneal Fibrosis
Session Information
- Peritoneal Dialysis: Inflammation, Peritoneal Transport
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Authors
- Ishimura, Takuya, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Ishii, Akira, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Osaki, Keisuke, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Toda, Naohiro, Kansai Electric Power Hospital, Osaka, Japan
- Mori, Keita P., Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Handa, Takaya, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Yanagita, Motoko, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Yokoi, Hideki, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Background
Peritoneal fibrosis is one of major characteristics of peritoneal membrane damage. Our group previously reported highly upregulated genes in the peritoneal membrane from chlorhexidine gluconate (CG)-treated peritoneal fibrosis mice compared with control in microarray analysis, one of which was matrix metalloproteinase-10 (MMP-10). MMP-10 was a proteinase protein degrading components of extracellular matrix (ECM) and was known to be associated with arteriosclerosis or tissue repair. Although deletion of MMP-2 and MMP-9, which were called gelatinases, ameliorated peritoneal fibrosis, the role of MMP-10 has not been elucidated in peritoneal fibrosis yet.
Methods
To investigate the role of MMP-10 in peritoneal fibrosis, we induced peritoneal fibrosis by intraperitoneal injection of chlorhexidine gluconate in wild-type (WT) and MMP-10 knockout (KO) mice. We administrated 0.01 mL/gBW of 0.1% CG in 15% ethanol and 85% phosphate-buffered saline (PBS) 3 times per week for 4 weeks. Control mice received intraperitoneal injection of PBS. Peritoneal sections were stained with Masson’s trichrome and were analyzed by immunohistochemical study.
Results
We identified upregulation of MMP-10 by 8.6-times in the peritoneum from CG-treated WT mice by a microarray analysis. There were no histological changes in the peritoneum between PBS-treated WT mice and PBS-treated MMP-10 KO mice. CG-treated WT mice had a remarkable thickening of peritoneum, an increased number of αSMA-, F4/80-positive cells in the peritoneum, and upregulation of MMP-10 mainly within the mesothelial cells and fibroblasts in the submesothelial area of the peritoneum. In contrast, CG-treated MMP-10 KO mice showed reduction of peritoneal thickness and accumulation of αSMA-, F4/80-positive cells in the peritoneum. Furthermore, the peritoneal enhanced expression of Tgfb1, Col1a1, Ctgf, and Ccl2 (MCP1) in WT mice was remarkably reduced in MMP-10 KO mice.
Conclusion
These results indicate that MMP-10 is upregulated in mesothelial cells and fibroblasts in peritoneal injury and can aggravate peritoneal fibrosis. Therefore, inhibition of MMP-10 could become a therapeutic strategy in peritoneal fibrosis.