ArticlePloS one2018
Deubiquitinase inhibitor PR-619 reduces Smad4 expression and suppresses renal fibrosis in mice with unilateral ureteral obstruction.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- The Ubiquitin-Specific Protease Family: Master Regulators of Renal Fibrosis Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2026Review
- The Role of Deubiquitinating Enzymes in Primary Bone Cancer.Molecular biotechnology · 2025Review
- Renal fibrosis progression following partial unilateral ureteral obstruction: mechanisms and therapeutic insights.World journal of urology · 2025Review
- Native Mass Spectrometry Reveals Binding Interactions of SARS-CoV-2 PLpro with Inhibitors and Cellular Targets.ACS infectious diseases · 2024Article
- TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review).Molecular medicine reports · 2024Review
- Reno-protective effect of protocatechuic acid is independent of sex-related differences in murine model of UUO-induced kidney injury.Pharmacological reports : PR · 2024Article
- Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation.International journal of molecular sciences · 2023Review
- Anti-tumor effects of deubiquitinating enzyme inhibitor PR-619 in human chondrosarcoma through reduced cell proliferation and endoplasmic reticulum stress-related apoptosis.American journal of cancer research · 2023Article
- The Protective Effect of Zebularine, an Inhibitor of DNA Methyltransferase, on Renal Tubulointerstitial Inflammation and Fibrosis.International journal of molecular sciences · 2022Article
- Inhibition of Ubiquitin-specific Protease 4 Attenuates Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via Transforming Growth Factor Beta Receptor Type I.Current medical science · 2022Article
- CircACTR2 in macrophages promotes renal fibrosis by activating macrophage inflammation and epithelial-mesenchymal transition of renal tubular epithelial cells.Cellular and molecular life sciences : CMLS · 2022Article
- Extracellular Vesicles in Redox Signaling and Metabolic Regulation in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2022Review
- USP10 Promotes Fibronectin Recycling, Secretion, and Organization.Investigative ophthalmology & visual science · 2021Article
- Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.PloS one · 2021Article
- Article
- Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma.Cell proliferation · 2021Article
- USP10 Targeted Self-Deliverable siRNA to Prevent Scarring in the Cornea.Molecular therapy. Nucleic acids · 2020Article
- Smad4-dependent morphogenic signals control the maturation and axonal targeting of basal vomeronasal sensory neurons to the accessory olfactory bulb.Development (Cambridge, England) · 2020Article
- Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments.Biomolecules · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deubiquitinating enzymes (DUBs) remove ubiquitin from their substrates and, together with ubiquitin ligases, play an important role in the regulation of protein expression. Although transforming growth factor (TGF)-β1-Smad signaling is a central pathway of renal fibrosis, the role of DUBs in the expression of TGF-β receptors and Smads during the development of renal fibrosis remains unknown. In this study, we investigated whether PR-619, a pan-DUB inhibitor, suppresses fibrosis in mice with unilateral ureteral obstruction (UUO) and TGF-β1-stimulated normal rat kidney (NRK)-49F cells, a rat renal fibroblast cell line. Either the vehicle (dimethyl sulfoxide) or PR-619 (100 μg) was intraperitoneally administered to mice after UUO induction once a day for 7 days. Administration of PR-619 attenuated renal fibrosis with downregulation of mesenchymal markers, extracellular matrix proteins, matrix metalloproteinases, apoptosis, macrophage infiltration, and the TGF-β1 mRNA level in UUO mice. Although type I TGF-β receptor (TGF-βRI), Smad2, Smad3, and Smad4 protein expression levels were markedly increased in mice with UUO, administration of PR-619 suppressed only Smad4 expression but not TGF-βRI, Smad2, or Smad3 expression. PR-619 also had an inhibitory effect on TGF-β1-induced α-smooth muscle actin expression and reduced Smad4 levels in NRK-49F cells. Our results indicate that PR-619 ameliorates renal fibrosis, which is accompanied by the reduction of Smad4 expression.
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