Inhibitory effects of matrix metalloproteinase inhibitor ONO-4817 on morphological alterations in chlorhexidine gluconate-induced peritoneal sclerosis rats

Ro, Yuuki; Hamada, Chikuma; Inaba, Masanori; Io, Hiroaki; Kaneko, Kayo; Tomino, Yasuhiko

doi:10.1093/ndt/gfm323

Cited by 46 publications

(44 citation statements)

References 16 publications

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“…Ro et al have reported that the MMP inhibitor ONO-4817 controlled angiogenesis, infiltration of macrophage, and peritoneal fibrosis in rat models of peritoneal sclerosis [10], which suggests the possibility of protection from peritoneal injury by inhibition of MMP-2 activities. Angiotensin-converting enzyme (ACE) inhibitors have been shown to have inhibitory effects on MMP-2 activity [45,46].…”

Section: Protection From Peritoneal Injury By Inhibition Of Mmp-2mentioning

confidence: 98%

“…In rodent models of peritoneal injury, the development of EPS was analyzed by injecting the antiseptic chlorhexidine gluconate into the peritoneal cavity to induce inflammation [7][8][9][10][11]. In this model, MMP-2 levels in the peritoneal effluent and MMP-2 gene expression in the peritoneum correlated with changes in thickness of the peritoneum, inflammation, D/D0 glucose levels, and net ultrafiltration.…”

Section: Production Of Mmp-2 In Animal Models Of Peritoneal Injurymentioning

confidence: 99%

“…Gene expression analysis and/or immunohistochemistry analysis revealed that MMP-2, MT1-MMP, and TIMP-2 are produced in the peritoneal tissue [7][8][9][10][11][12][13]25]. MMP-2 is produced by peritoneal cells, such as macrophages, mesenchymal cells, endothelial cells, and mesothelial cells (Figures 3 and 4, Table).…”

Section: Production Of Mmp-2 In the Peritoneummentioning

confidence: 99%

“…[44], which may explain why drainage levels of MMP-2 reflects the peritoneal transport ratio. Activated mesenchymal cells, such as myofibroblasts or fibroblasts, synthesize ECM proteins or migrate during the disassemble of ECM of the peritoneum by MMP-2 or other proteinases [8][9][10][11][12]33]. Presence of excessive ECM proteins, such as collagen, leads to peritoneal fibrosis with peritoneal thickening and promotes the production of MMP-2 by myofibroblasts [9].…”

Section: Production Of Mmp-2 In the Peritoneummentioning

confidence: 99%

“…Presence of excessive ECM proteins, such as collagen, leads to peritoneal fibrosis with peritoneal thickening and promotes the production of MMP-2 by myofibroblasts [9]. In addition, neomicrovascularization may occur while ECM is being degraded by MMP-2 produced by activated endothelial cells in the microvasculature [10,12,33]. According to the results of D/S ratio analysis, most MMP-2 in the peritoneal effluent is not transported from the circulation [26].…”

Section: Production Of Mmp-2 In the Peritoneummentioning

confidence: 99%

See 4 more Smart Citations

Matrix Metalloproteinases Cause Peritoneal Injury in Peritoneal Dialysis

Hirahara¹,

Akimoto²,

Morishita³

et al. 2011

Progress in Peritoneal Dialysis

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Section: Protection From Peritoneal Injury By Inhibition Of Mmp-2mentioning

confidence: 98%

Section: Production Of Mmp-2 In Animal Models Of Peritoneal Injurymentioning

confidence: 99%

Section: Production Of Mmp-2 In the Peritoneummentioning

confidence: 99%

Section: Production Of Mmp-2 In the Peritoneummentioning

confidence: 99%

Section: Production Of Mmp-2 In the Peritoneummentioning

confidence: 99%

See 3 more Smart Citations

Matrix Metalloproteinases Cause Peritoneal Injury in Peritoneal Dialysis

Hirahara¹,

Akimoto²,

Morishita³

et al. 2011

Progress in Peritoneal Dialysis

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Mechanisms and interventions in peritoneal fibrosis

Tomino

2011

Clin Exp Nephrol

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Peritoneal dialysis (PD) is an attractive treatment for patients with end-stage kidney disease (ESKD). However, long-term peritoneal dialysis is associated with development of functional and structural alterations of the peritoneal membrane. Several factors are implicated in the development of peritoneal fibrosis in PD patients. Inflammatory cytokines, which are induced in the peritoneal cavity during peritonitis, may also induce chronic inflammation and fibrosis. Transforming growth factor β1 (TGF-β1) is generally considered to play an important role in peritoneal fibrosis. The objective of this review is to summarize the mechanisms of peritoneal fibrosis using in vitro and in vivo studies, and the current status and future prospects of interventions in the peritoneal fibrosis.

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Identifying simultaneous matrix metalloproteinases/soluble epoxide hydrolase inhibitors

et al. 2022

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Matrix metalloproteinase (MMP) and soluble epoxide hydrolase (sEH) have completely unrelated biological functions, however, their dysregulation produce similar effects on biological systems. Based on the similarity in the reported structural requirements for their inhibition, the current study aimed to identify a simultaneous inhibitor for MMP and sEH. Six compounds were identi ed as potential simultaneous MMP/sEH inhibitors and tested for their capacity to inhibit MMP and sEH. Inhibition of MMP and sEH activity using their endogenous and exogenous substrates was measured by liquid chromatography/mass spectrometry, spectrophotometry and zymography. Two compounds, CTK8G1143 and ONO-4817, were identi ed to inhibit both MMP and sEH activity. CTK8G1143 and ONO-4817 inhibited the recombinant human sEH activity by an average of 67.4% and 55.2%, respectively. The IC 50 for CTK8G1143 and ONO-4817 to inhibit recombinant human sEH were 5.2 and 3.5 µM, respectively, whereas, their maximal inhibition values were 71.4% and 42.8%, respectively. Also, MMP and sEH activity of human cardiomyocytes were simultaneously inhibited by CTK8G1143 and ONO-4817. Regarding other compounds, they showed either MMP or sEH inhibitory activity but not both. In conclusion, these two simultaneous inhibitors of MMP and sEH could provide a promising intervention for the prevention and control of several diseases, especially cardiovascular diseases.

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Inhibitory effects of matrix metalloproteinase inhibitor ONO-4817 on morphological alterations in chlorhexidine gluconate-induced peritoneal sclerosis rats

Abstract: It appears that the administration of the MMP inhibitor ONO-4817 might be a new approach to the amelioration of PS.

Cited by 46 publications

References 16 publications

Matrix Metalloproteinases Cause Peritoneal Injury in Peritoneal Dialysis

Matrix Metalloproteinases Cause Peritoneal Injury in Peritoneal Dialysis

Mechanisms and interventions in peritoneal fibrosis

Identifying simultaneous matrix metalloproteinases/soluble epoxide hydrolase inhibitors

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