ArticlePeritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Pyrrole-imidazole polyamide targeting transforming growth factor β1 ameliorates encapsulating peritoneal sclerosis.
Article in Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 7 citations in OpenAlex.
- Effects of Pyrrole-Imidazole Polyamides Targeting Human TGF-β1 on the Malignant Phenotypes of Liver Cancer Cells.Molecules (Basel, Switzerland) · 2020Article
- Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy.Molecules (Basel, Switzerland) · 2020Article
- Preclinical Study of DNA-Recognized Peptide Compound Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Progressive Renal Diseases in the Common Marmoset.Molecules (Basel, Switzerland) · 2019Article
- The past and presence of gene targeting: from chemicals and DNA via proteins to RNA.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
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7 authors at 1 institution in 1 country.
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Abstract
objectiveEncapsulating peritoneal sclerosis (EPS) is a devastating fibrotic complication in patients treated with peritoneal dialysis (PD). Transforming growth factor β1 (TGF-β1) is a pivotal factor in the induction of EPS.
methodsTo develop pyrrole-imidazole (PI) polyamide, a novel gene silencer, targeted to the TGF-β1 promoter (Polyamide) for EPS, we examined the effects of Polyamide on messenger RNA (mRNA) expression of TGF-β1, vascular endothelial growth factor (VEGF), and extracellular matrix (ECM) in mesothelial cells in vitro, and on the thickness of injured peritoneum evaluated by histology and high-resolution regional elasticity mapping in rats in vivo.
resultsPolyamide significantly lowered mRNA expression of TGF-β1 and ECM in vitro. Polyamide labeled with fluorescein isothiocyanate was taken up into the injured peritoneum and was strongly localized in the nuclei of most cells. Polyamide 1 mg was injected intraperitoneally 1 or 3 times in rats receiving a daily intraperitoneal injection of chlorhexidine gluconate and ethanol (CHX) for 14 days. Polyamide significantly suppressed peritoneal thickening and the abundance of TGF-β1 and fibronectin mRNA, but did not affect expression of VEGF mRNA in the injured peritoneum. Elasticity distribution mapping showed that average elasticity was significantly lower in Polyamide-treated rats than in rats treated solely with CHX.
conclusionsPolyamide suppressed the stiffness, ECM formation, and thickening of the injured peritoneum that occurs during EPS pathogenesis. These data suggest that PI polyamide targeted to the TGF-β1 promoter will be a specific and feasible therapeutic strategy for patients with EPS.
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